Details
| Stereochemistry | MIXED |
| Molecular Formula | C35H38Cl2N8O4.3ClH |
| Molecular Weight | 815.016 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 2 / 3 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.Cl.CCC(C)N1N=CN(C1=O)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(OC[C@H]5CO[C@@](CN6C=NC=N6)(O5)C7=C(Cl)C=C(Cl)C=C7)C=C4
InChI
InChIKey=IKQCHGBROJMCCD-MEBRADKNSA-N
InChI=1S/C35H38Cl2N8O4.3ClH/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37;;;/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3;3*1H/t25?,31-,35-;;;/m0.../s1
| Molecular Formula | C35H38Cl2N8O4 |
| Molecular Weight | 705.633 |
| Charge | 0 |
| Count |
|
| Stereochemistry | EPIMERIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 3 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
SPORANOX is the brand name for itraconazole, an azole antifungal agent. Itraconazole is a 1:1:1:1 racemic mixture of four diastereomers (two enantiomeric pairs), each possessing three chiral centers. In vitro studies have demonstrated that itraconazole inhibits the cytochrome P450-dependent synthesis of ergosterol, which is a vital component of fungal cell membranes. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis. SPORANOX capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary; Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis, and Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy. SPORANOX is also indicated for the treatment of the following fungal infections in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium), and Onychomycosis of the fingernail due to dermatophytes (tinea unguium). Itraconazole is mainly metabolized through CYP3A4. Other drugs that either share this metabolic pathway or modify CYP3A4 activity may influence the pharmacokinetics of itraconazole. Similarly, itraconazole may modify the pharmacokinetics of other drugs that share this metabolic pathway. Itraconazole is a potent CYP3A4 inhibitor and a P-glycoprotein inhibitor. When using concomitant medication, it is recommended that the corresponding label be consulted for information on the route of metabolism and the possible need to adjust dosages.
CNS Activity
Curator's Comment: Limited ability to cross the blood-brain barrier
https://books.google.ru/books?id=Qd_nCAAAQBAJ&pg=PA198&lpg=PA198&dq=ITRACONAZOLE+cross+blood-brain+barrier&source=bl&ots=gExVhzS3wQ&sig=M2Vea-eTPaedoDjCOCqfNT-Ftu0&hl=ru&sa=X&ved=0ahUKEwi21cbW4PbPAhVGuhoKHXGhDk44ChDoAQgbMAA#v=onepage&q=ITRACONAZOLE%20cross%20blood-brain%20barrier&f=false
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL1780 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | SPORANOX Approved UseSPORANOX® (itraconazole) Capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis, and Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy. Specimens for fungal cultures and other relevant laboratory studies (wet mount, histopathology, serology) should be obtained before therapy to isolate and identify causative organisms. Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, antiinfective therapy should be adjusted accordingly. SPORANOX® Capsules are also indicated for the treatment of the following fungal infections in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium), and Onychomycosis of the fingernail due to dermatophytes (tinea unguium). Prior to initiating treatment, appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis. (See CLINICAL PHARMACOLOGY: Special Populations, CONTRAINDICATIONS, WARNINGS, and ADVERSE REACTIONS: Post-marketing Experience for more information.) Description of Clinical Studies Blastomycosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=73 combined) in patients with normal or abnormal immune status. The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 6 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of blastomycosis compared with the natural history of untreated cases. Histoplasmosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=34 combined) in patients with normal or abnormal immune status (not including HIV-infected patients). The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 12 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of histoplasmosis, compared with the natural history of untreated cases. Histoplasmosis in HIV-infected patients Data from a small number of HIV-infected patients suggested that the response rate of histoplasmosis in HIV-infected patients is similar to that of non-HIV-infected patients. The clinical course of histoplasmosis in HIV-infected patients is more severe and usually requires maintenance therapy to prevent relapse. Aspergillosis Analyses were conducted on data from an open-label, single-patient-use protocol designed to make itraconazole available in the U.S. for patients who either failed or were intolerant of amphotericin B therapy (N=190). The findings were corroborated by two smaller open-label studies (N=31 combined) in the same patient population. Most adult patients were treated with a daily dose of 200 to 400 mg, with a median duration of 3 months. Results of these studies demonstrated substantial evidence of effectiveness of itraconazole as a second-line therapy for the treatment of aspergillosis compared with the natural history of the disease in patients who either failed or were intolerant of amphotericin B therapy. Onychomycosis of the toenail Analyses were conducted on data from three double-blind, placebo-controlled studies (N=214 total; 110 given SPORANOX® Capsules) in which patients with onychomycosis of the toenails received 200 mg of SPORANOX® Capsules once daily for 12 consecutive weeks. Results of these studies demonstrated mycologic cure, defined as simultaneous occurrence of negative KOH plus negative culture, in 54% of patients. Thirty-five percent (35%) of patients were considered an overall success (mycologic cure plus clear or minimal nail involvement with significantly decreased signs) and 14% of patients demonstrated mycologic cure plus clinical cure (clearance of all signs, with or without residual nail deformity). The mean time to overall success was approximately 10 months. Twenty-one percent (21%) of the overall success group had a relapse (worsening of the global score or conversion of KOH or culture from negative to positive). Onychomycosis of the fingernail Analyses were conducted on data from a double-blind, placebo-controlled study (N=73 total; 37 given SPORANOX® Capsules) in which patients with onychomycosis of the fingernails received a 1-week course (pulse) of 200 mg of SPORANOX® Capsules b.i.d., followed by a 3-week period without SPORANOX®, which was followed by a second 1-week pulse of 200 mg of SPORANOX® Capsules b.i.d. Results demonstrated mycologic cure in 61% of patients. Fifty-six percent (56%) of patients were considered an overall success and 47% of patients demonstrated mycologic cure plus clinical cure. The mean time to overall success was approximately 5 months. None of the patients who achieved overall success relapsed. Launch Date1992 |
|||
| Curative | SPORANOX Approved UseSPORANOX® (itraconazole) Capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis, and Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy. Specimens for fungal cultures and other relevant laboratory studies (wet mount, histopathology, serology) should be obtained before therapy to isolate and identify causative organisms. Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, antiinfective therapy should be adjusted accordingly. SPORANOX® Capsules are also indicated for the treatment of the following fungal infections in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium), and Onychomycosis of the fingernail due to dermatophytes (tinea unguium). Prior to initiating treatment, appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis. (See CLINICAL PHARMACOLOGY: Special Populations, CONTRAINDICATIONS, WARNINGS, and ADVERSE REACTIONS: Post-marketing Experience for more information.) Description of Clinical Studies Blastomycosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=73 combined) in patients with normal or abnormal immune status. The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 6 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of blastomycosis compared with the natural history of untreated cases. Histoplasmosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=34 combined) in patients with normal or abnormal immune status (not including HIV-infected patients). The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 12 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of histoplasmosis, compared with the natural history of untreated cases. Histoplasmosis in HIV-infected patients Data from a small number of HIV-infected patients suggested that the response rate of histoplasmosis in HIV-infected patients is similar to that of non-HIV-infected patients. The clinical course of histoplasmosis in HIV-infected patients is more severe and usually requires maintenance therapy to prevent relapse. Aspergillosis Analyses were conducted on data from an open-label, single-patient-use protocol designed to make itraconazole available in the U.S. for patients who either failed or were intolerant of amphotericin B therapy (N=190). The findings were corroborated by two smaller open-label studies (N=31 combined) in the same patient population. Most adult patients were treated with a daily dose of 200 to 400 mg, with a median duration of 3 months. Results of these studies demonstrated substantial evidence of effectiveness of itraconazole as a second-line therapy for the treatment of aspergillosis compared with the natural history of the disease in patients who either failed or were intolerant of amphotericin B therapy. Onychomycosis of the toenail Analyses were conducted on data from three double-blind, placebo-controlled studies (N=214 total; 110 given SPORANOX® Capsules) in which patients with onychomycosis of the toenails received 200 mg of SPORANOX® Capsules once daily for 12 consecutive weeks. Results of these studies demonstrated mycologic cure, defined as simultaneous occurrence of negative KOH plus negative culture, in 54% of patients. Thirty-five percent (35%) of patients were considered an overall success (mycologic cure plus clear or minimal nail involvement with significantly decreased signs) and 14% of patients demonstrated mycologic cure plus clinical cure (clearance of all signs, with or without residual nail deformity). The mean time to overall success was approximately 10 months. Twenty-one percent (21%) of the overall success group had a relapse (worsening of the global score or conversion of KOH or culture from negative to positive). Onychomycosis of the fingernail Analyses were conducted on data from a double-blind, placebo-controlled study (N=73 total; 37 given SPORANOX® Capsules) in which patients with onychomycosis of the fingernails received a 1-week course (pulse) of 200 mg of SPORANOX® Capsules b.i.d., followed by a 3-week period without SPORANOX®, which was followed by a second 1-week pulse of 200 mg of SPORANOX® Capsules b.i.d. Results demonstrated mycologic cure in 61% of patients. Fifty-six percent (56%) of patients were considered an overall success and 47% of patients demonstrated mycologic cure plus clinical cure. The mean time to overall success was approximately 5 months. None of the patients who achieved overall success relapsed. Launch Date1992 |
|||
| Curative | SPORANOX Approved UseSPORANOX® (itraconazole) Capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis, and Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy. Specimens for fungal cultures and other relevant laboratory studies (wet mount, histopathology, serology) should be obtained before therapy to isolate and identify causative organisms. Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, antiinfective therapy should be adjusted accordingly. SPORANOX® Capsules are also indicated for the treatment of the following fungal infections in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium), and Onychomycosis of the fingernail due to dermatophytes (tinea unguium). Prior to initiating treatment, appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis. (See CLINICAL PHARMACOLOGY: Special Populations, CONTRAINDICATIONS, WARNINGS, and ADVERSE REACTIONS: Post-marketing Experience for more information.) Description of Clinical Studies Blastomycosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=73 combined) in patients with normal or abnormal immune status. The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 6 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of blastomycosis compared with the natural history of untreated cases. Histoplasmosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=34 combined) in patients with normal or abnormal immune status (not including HIV-infected patients). The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 12 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of histoplasmosis, compared with the natural history of untreated cases. Histoplasmosis in HIV-infected patients Data from a small number of HIV-infected patients suggested that the response rate of histoplasmosis in HIV-infected patients is similar to that of non-HIV-infected patients. The clinical course of histoplasmosis in HIV-infected patients is more severe and usually requires maintenance therapy to prevent relapse. Aspergillosis Analyses were conducted on data from an open-label, single-patient-use protocol designed to make itraconazole available in the U.S. for patients who either failed or were intolerant of amphotericin B therapy (N=190). The findings were corroborated by two smaller open-label studies (N=31 combined) in the same patient population. Most adult patients were treated with a daily dose of 200 to 400 mg, with a median duration of 3 months. Results of these studies demonstrated substantial evidence of effectiveness of itraconazole as a second-line therapy for the treatment of aspergillosis compared with the natural history of the disease in patients who either failed or were intolerant of amphotericin B therapy. Onychomycosis of the toenail Analyses were conducted on data from three double-blind, placebo-controlled studies (N=214 total; 110 given SPORANOX® Capsules) in which patients with onychomycosis of the toenails received 200 mg of SPORANOX® Capsules once daily for 12 consecutive weeks. Results of these studies demonstrated mycologic cure, defined as simultaneous occurrence of negative KOH plus negative culture, in 54% of patients. Thirty-five percent (35%) of patients were considered an overall success (mycologic cure plus clear or minimal nail involvement with significantly decreased signs) and 14% of patients demonstrated mycologic cure plus clinical cure (clearance of all signs, with or without residual nail deformity). The mean time to overall success was approximately 10 months. Twenty-one percent (21%) of the overall success group had a relapse (worsening of the global score or conversion of KOH or culture from negative to positive). Onychomycosis of the fingernail Analyses were conducted on data from a double-blind, placebo-controlled study (N=73 total; 37 given SPORANOX® Capsules) in which patients with onychomycosis of the fingernails received a 1-week course (pulse) of 200 mg of SPORANOX® Capsules b.i.d., followed by a 3-week period without SPORANOX®, which was followed by a second 1-week pulse of 200 mg of SPORANOX® Capsules b.i.d. Results demonstrated mycologic cure in 61% of patients. Fifty-six percent (56%) of patients were considered an overall success and 47% of patients demonstrated mycologic cure plus clinical cure. The mean time to overall success was approximately 5 months. None of the patients who achieved overall success relapsed. Launch Date1992 |
|||
| Curative | SPORANOX Approved UseSPORANOX® (itraconazole) Capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis, and Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy. Specimens for fungal cultures and other relevant laboratory studies (wet mount, histopathology, serology) should be obtained before therapy to isolate and identify causative organisms. Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, antiinfective therapy should be adjusted accordingly. SPORANOX® Capsules are also indicated for the treatment of the following fungal infections in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium), and Onychomycosis of the fingernail due to dermatophytes (tinea unguium). Prior to initiating treatment, appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis. (See CLINICAL PHARMACOLOGY: Special Populations, CONTRAINDICATIONS, WARNINGS, and ADVERSE REACTIONS: Post-marketing Experience for more information.) Description of Clinical Studies Blastomycosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=73 combined) in patients with normal or abnormal immune status. The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 6 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of blastomycosis compared with the natural history of untreated cases. Histoplasmosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=34 combined) in patients with normal or abnormal immune status (not including HIV-infected patients). The median dose was 200 mg/day. A response for most signs and symptoms was observed within the first 2 weeks, and all signs and symptoms cleared between 3 and 12 months. Results of these two studies demonstrated substantial evidence of the effectiveness of itraconazole for the treatment of histoplasmosis, compared with the natural history of untreated cases. Histoplasmosis in HIV-infected patients Data from a small number of HIV-infected patients suggested that the response rate of histoplasmosis in HIV-infected patients is similar to that of non-HIV-infected patients. The clinical course of histoplasmosis in HIV-infected patients is more severe and usually requires maintenance therapy to prevent relapse. Aspergillosis Analyses were conducted on data from an open-label, single-patient-use protocol designed to make itraconazole available in the U.S. for patients who either failed or were intolerant of amphotericin B therapy (N=190). The findings were corroborated by two smaller open-label studies (N=31 combined) in the same patient population. Most adult patients were treated with a daily dose of 200 to 400 mg, with a median duration of 3 months. Results of these studies demonstrated substantial evidence of effectiveness of itraconazole as a second-line therapy for the treatment of aspergillosis compared with the natural history of the disease in patients who either failed or were intolerant of amphotericin B therapy. Onychomycosis of the toenail Analyses were conducted on data from three double-blind, placebo-controlled studies (N=214 total; 110 given SPORANOX® Capsules) in which patients with onychomycosis of the toenails received 200 mg of SPORANOX® Capsules once daily for 12 consecutive weeks. Results of these studies demonstrated mycologic cure, defined as simultaneous occurrence of negative KOH plus negative culture, in 54% of patients. Thirty-five percent (35%) of patients were considered an overall success (mycologic cure plus clear or minimal nail involvement with significantly decreased signs) and 14% of patients demonstrated mycologic cure plus clinical cure (clearance of all signs, with or without residual nail deformity). The mean time to overall success was approximately 10 months. Twenty-one percent (21%) of the overall success group had a relapse (worsening of the global score or conversion of KOH or culture from negative to positive). Onychomycosis of the fingernail Analyses were conducted on data from a double-blind, placebo-controlled study (N=73 total; 37 given SPORANOX® Capsules) in which patients with onychomycosis of the fingernails received a 1-week course (pulse) of 200 mg of SPORANOX® Capsules b.i.d., followed by a 3-week period without SPORANOX®, which was followed by a second 1-week pulse of 200 mg of SPORANOX® Capsules b.i.d. Results demonstrated mycologic cure in 61% of patients. Fifty-six percent (56%) of patients were considered an overall success and 47% of patients demonstrated mycologic cure plus clinical cure. The mean time to overall success was approximately 5 months. None of the patients who achieved overall success relapsed. Launch Date1992 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
658.1 ng/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
116.8 ng/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
213 μg/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
162 ng/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
332 ng/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
974.2 ng/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
HYDROXYITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
221.7 ng/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
264 ng/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
9046.81 ng × h/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
905.09 ng × h/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
3.34 ng × h/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
2.27 μg × h/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7.05 μg × h/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
19054.95 ng × h/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
HYDROXYITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
2538.33 ng × h/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
4.58 μg × h/mL |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
36.84 h |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
36.84 h |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
20.06 h |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
HYDROXYITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
20.06 h |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.2% |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
0.2% |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
0.2% |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
0.2% |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
ITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.5% |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
0.5% |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
HYDROXYITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
0.5% |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
|
0.5% |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
HYDROXYITRACONAZOLE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
2.5 mg/kg single, intravenous Dose: 2.5 mg/kg Route: intravenous Route: single Dose: 2.5 mg/kg Sources: |
unhealthy, 0.5 - 16 years n = 33 Health Status: unhealthy Condition: risk for fungal infection Age Group: 0.5 - 16 years Sex: M+F Population Size: 33 Sources: |
|
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Co-administed with:: hydroxypropyl-beta-cyclodextrin(0.1 g/kg) Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
Other AEs: Depression... Other AEs: Depression (2%) Sources: |
100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
Other AEs: Nausea, Diarrhea... Other AEs: Nausea (11%) Sources: Diarrhea (11%) Vomiting (7%) Abdominal pain (6%) Constipation (2%) Fever (7%) Chest pain (3%) Pain (2%) Fatigue (2%) Coughing (4%) Dyspnea (2%) Pneumonia (2%) Sinusitis (2%) Sputum increased (2%) Rash (4%) Sweating increased (3%) Skin and subcutaneous tissue disorders (2%) Headache (4%) Dizziness (2%) Pneumocystis carinii infection (2%) |
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Condition: tinea Age Group: adult Sex: unknown Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Depression | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Co-administed with:: hydroxypropyl-beta-cyclodextrin(0.1 g/kg) Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Diarrhea | 11% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Nausea | 11% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Constipation | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Dizziness | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Dyspnea | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Fatigue | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Pain | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Pneumocystis carinii infection | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Pneumonia | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Sinusitis | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Skin and subcutaneous tissue disorders | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Sputum increased | 2% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Chest pain | 3% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Sweating increased | 3% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Coughing | 4% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Headache | 4% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Rash | 4% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Abdominal pain | 6% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Fever | 7% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
| Vomiting | 7% | 100 mg 2 times / day steady, oral Recommended Dose: 100 mg, 2 times / day Route: oral Route: steady Dose: 100 mg, 2 times / day Sources: |
unhealthy, adult n = 350 Health Status: unhealthy Condition: HIV and oropharyngeal or esophageal candidiasis Age Group: adult Sex: unknown Population Size: 350 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| strong [IC50 0.0004 uM] | ||||
| strong [IC50 0.007 uM] | ||||
| strong [IC50 0.0326 uM] | yes (co-administration study) Comment: [PMID:15242978]: unbound Ki = 1.3 nM; unbound IC50 = 6.1 nM |
|||
| strong [IC50 2 uM] | ||||
| strong [IC50 2 uM] | ||||
| strong [IC50 2 uM] | weak (co-administration study) Comment: Itraconazole increased the mean area under the plasma concentration-time curve [AUC (0-9)] of morphine by 29% (P=0.002), its AUC (0-48) by 22% (P=0.013) and its peak plasma concentration by 28% |
|||
| strong [Ki 0.0144 uM] | ||||
| yes [IC50 >10 uM] | ||||
| yes [IC50 >10 uM] | ||||
| yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes |
PubMed
| Title | Date | PubMed |
|---|---|---|
| The use of itraconazole to treat cutaneous fungal infections in children. | 1999 |
|
| Activity of pradimicin BMS-181184 against Aspergillus spp. | 1999 Aug |
|
| Comparisons of the effects of fungicidal and fungistatic antifungal agents on the morphogenetic transformation of Candida albicans. | 1999 Mar |
|
| Randomized double-blind comparison of short-term itraconazole and terbinafine therapy for toenail onychomycosis. | 1999 May |
|
| In-vitro activity of voriconazole (UK-109,496), LY303366 and other antifungal agents against oral Candida spp. isolates from HIV-infected patients. | 1999 Nov |
|
| Novel antifungals based on 4-substituted imidazole: solid-phase synthesis of substituted aryl sulfonamides towards optimization of in vitro activity. | 2000 Dec 18 |
|
| Clinical activity of the new triazole drug voriconazole (UK 109, 496) against disseminated hepatosplenic aspergillosis in a patient with relapsed leukemia. | 2001 |
|
| Penicillium marneffei: types and drug susceptibility. | 2001 |
|
| The cost of treating systemic fungal infections. | 2001 |
|
| DNA fingerprinting of serial Candida albicans isolates obtained during itraconazole prophylaxis in patients with AIDS. | 2001 Apr |
|
| Effect of clarithromycin and itraconazole on the pharmacokinetics of ropivacaine. | 2001 Apr |
|
| A molecular epidemiological study of sequential oral isolates of Candida albicans from terminally ill patients. | 2001 Apr |
|
| In vitro activity of propyl gallate-azole drug combination against fluconazole- and itraconazole-resistant Candida albicans strains. | 2001 Apr |
|
| Subcutaneous phaeohyphomycotic cysts caused by Exophiala jeanselmei in a lung transplant patient. | 2001 Apr |
|
| A case of cutaneous ulcerative alternariosis: rare association with diabetes mellitus and unusual failure of itraconazole treatment. | 2001 Apr 15 |
|
| Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species. | 2001 Feb |
|
| Phaeohyphomycosis due to Cladosporium cladosporioides. | 2001 Feb |
|
| Cutaneous alternariosis in a cardiac transplant recipient. | 2001 Feb |
|
| Lymphadenitis caused by Scedosporium apiospermum in an immunocompetent patient. | 2001 Feb 1 |
|
| Treating onychomycosis. | 2001 Feb 15 |
|
| Itraconazole: an effective oral antifungal for onychomycosis. | 2001 Jan |
|
| Systemic antifungal therapy. | 2001 Jan |
|
| Recalcitrant trichophytic granuloma associated with NK-cell deficiency in a SLE patient treated with corticosteroid. | 2001 Jan-Feb |
|
| Oropharyngeal candidiasis in patients with human immunodeficiency virus: correlation of clinical outcome with in vitro resistance, serum azole levels, and immunosuppression. | 2001 Jun 1 |
|
| Long-term follow-up study of onychomycosis: cure rate and dropout rate with oral antifungal treatments. | 2001 Mar |
|
| Trends in frequency and susceptibilities of Candida glabrata bloodstream isolates at a university hospital. | 2001 Mar |
|
| Oral antifungals as prophylaxis in haematological malignancy. | 2001 Mar |
|
| Malassezia pachydermatis fungaemia in a neonatal intensive care unit. | 2001 Mar |
|
| Impending rupture in an aortic arch aneurysm by Candida infection. | 2001 Mar |
|
| Single-blind, randomized, prospective study on terbinafine and itraconazole for treatment of dermatophyte toenail onychomycosis in the elderly. | 2001 Mar |
|
| Quantitation of itraconazole in rat heparinized plasma by liquid chromatography-mass spectrometry. | 2001 Mar 5 |
|
| Cervical manifestation of blastomycosis. | 2001 Mar-Apr |
|
| Therapy for fungal infections in leukemia. | 2001 May |
|
| Itraconazole for treatment of sporotrichosis in a dog residing on a Christmas tree farm. | 2001 May 1 |
Sample Use Guides
Blastomycosis and Histoplasmosis:
The recommended dose is 200 mg once daily (2 capsules). If there is no obvious improvement, or there is evidence of progressive fungal disease, the dose should be increased in 100-mg increments to a maximum of 400 mg daily. Doses above 200 mg/day should be given in two divided doses.
Aspergillosis:
A daily dose of 200 to 400 mg is recommended. Treatment in Life-Threatening Situations: In life-threatening situations, a loading dose should be used. Although clinical studies did not provide for a loading dose, it is recommended, based on pharmacokinetic data, that a loading dose of 200 mg (2 capsules) three times daily (600 mg/day) be given for the first 3 days of treatment.
Onychomycosis: Toenails with or without fingernail involvement:
The recommended dose is 200 mg (2 capsules) once daily for 12 consecutive weeks.
Onychomycosis: Fingernails only:
The recommended dosing regimen is 2 treatment pulses, each consisting of
200 mg (2 capsules) b.i.d. (400 mg/day) for 1 week.
Route of Administration:
Oral
The growth inhibition effects of different concentrations of itraconazole ITC (2, 6, 15 µmol/L) was detected by CCK8 assay in KG1α and primary adult acute leukemia cells. Different concentrations of ITC for 7, 14 and 21 days were applied for observing the effect on colony formation. After 48 h treatments with 6 µmol/L ITC the morphological changes of cells were observed by Wright staining.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 15:16:54 GMT 2023
by
admin
on
Sat Dec 16 15:16:54 GMT 2023
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| Record UNII |
36RJ1K4UXZ
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| Record Status |
Validated (UNII)
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| Record Version |
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146019541
Created by
admin on Sat Dec 16 15:16:55 GMT 2023 , Edited by admin on Sat Dec 16 15:16:55 GMT 2023
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36RJ1K4UXZ
Created by
admin on Sat Dec 16 15:16:55 GMT 2023 , Edited by admin on Sat Dec 16 15:16:55 GMT 2023
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ACTIVE MOIETY |
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Volume of Distribution | PHARMACOKINETIC |
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