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Details

Stereochemistry ACHIRAL
Molecular Formula C19H24N4O2.CH4O3S
Molecular Weight 436.527
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PENTAMIDINE MONOMESYLATE

SMILES

C(CCOc1ccc(cc1)C(=N)N)CCOc2ccc(cc2)C(=N)N.CS(=O)(=O)O

InChI

InChIKey=LCNPURURRXMYET-UHFFFAOYSA-N
InChI=1S/C19H24N4O2.CH4O3S/c20-18(21)14-4-8-16(9-5-14)24-12-2-1-3-13-25-17-10-6-15(7-11-17)19(22)23;1-5(2,3)4/h4-11H,1-3,12-13H2,(H3,20,21)(H3,22,23);1H3,(H,2,3,4)

HIDE SMILES / InChI

Molecular Formula CH4O3S
Molecular Weight 96.1068
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C19H24N4O2
Molecular Weight 340.4202
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB00738 https://en.wikipedia.org/wiki/Pentamidine

Pentamidine (formulated as a salt, pentamidine diisethionate or dimesilate) is an antimicrobial medication given for prevention and treatment of pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii (formerly known as Pneumocystis carinii), a severe interstitial type of pneumonia often seen in patients with HIV infection. The drug is also the mainstay of treatment for stage I infection with Trypanosoma bruceigambiense (West African trypanosomiasis). Pentamidine is also used as a prophylactic against PCP in patients receiving chemotherapy and in some patients who have undergone organ transplantation, as they also have a depressed immune system as a direct side-effect of the drugs used. The mortality of untreated PCP is very high. Additionally, pentamidine has good clinical activity in treating leishmaniasis, and yeast infections caused by the organism Candida albicans. Pentamidine is also used as a prophylactic antibiotic for children undergoing treatment for leukemia. Studies suggest that the pentamidine isethionate interferes with microbial nuclear metabolism by inhibition of DNA, RNA, phospholipid and protein synthesis. However, the mode of action is not fully understood.

CNS Activity

Curator's Comment:: Pentamidine is able to cross the BBB, but a proportion is retained within the capillary endothelium. This may well explain its inability to treat well established CNS trypanosome infection. Furthermore, pentamidine movement into the CNS is a complex process involving multiple transporters.

Originator

Curator's Comment:: Pentamidine was first discovered by Ewins et al., as shown in U.S. Patent No. 2,277,861

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: O14717
Gene ID: 1787.0
Gene Symbol: TRDMT1
Target Organism: Homo sapiens (Human)
204.4 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
NEBUPENT

Approved Use

Pentamidine

Launch Date

4.82112012E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
751 nM
3.9 mg/kg 1 times / day multiple, intravenous
dose: 3.9 mg/kg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PENTAMIDINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
18.8 ng/mL
4 mg/kg 1 times / day multiple, irrigation
dose: 4 mg/kg
route of administration: Irrigation
experiment type: MULTIPLE
co-administered:
PENTAMIDINE unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
612 ng/mL
4 mg/kg single, intravenous
dose: 4 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PENTAMIDINE unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
6734 nM × h
3.9 mg/kg 1 times / day multiple, intravenous
dose: 3.9 mg/kg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
PENTAMIDINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.4 h
4 mg/kg single, intravenous
dose: 4 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PENTAMIDINE unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1600 mg single, intravenous
Overdose
unhealthy, 17
n = 1
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Age Group: 17
Population Size: 1
Sources:
Other AEs: Impaired renal function, Hepatic impairment...
Other AEs:
Impaired renal function
Hepatic impairment
Hypotension
Cardiopulmonary arrest
Sources:
600 mg 1 times / month multiple, respiratory
Highest studied dose
Dose: 600 mg, 1 times / month
Route: respiratory
Route: multiple
Dose: 600 mg, 1 times / month
Sources: Page: p.1167
unhealthy, 37.9 ± 7.5
n = 76
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Age Group: 37.9 ± 7.5
Sex: M+F
Population Size: 76
Sources: Page: p.1167
300 mg 1 times / month multiple, respiratory
Recommended
Dose: 300 mg, 1 times / month
Route: respiratory
Route: multiple
Dose: 300 mg, 1 times / month
Sources: Page: p.6
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources: Page: p.6
Disc. AE: Acute pancreatitis...
AEs leading to
discontinuation/dose reduction:
Acute pancreatitis
Sources: Page: p.6
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Disc. AE: Hypotension, Hypoglycemia...
Other AEs: Extravasation, Injection site ulceration...
AEs leading to
discontinuation/dose reduction:
Hypotension (grade 3-5)
Hypoglycemia (grade 5)
Acute pancreatitis (grade 5)
Cardiac arrhythmias (grade 5)
Cardiac arrhythmias (grade 5)
Other AEs:
Extravasation
Injection site ulceration
Injection site necrosis
Slough injection site
Sources:
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Disc. AE: Hypotension, Hypoglycemia...
Other AEs: Extravasation, Injection site ulceration...
AEs leading to
discontinuation/dose reduction:
Hypotension (grade 3-5)
Hypoglycemia (grade 5)
Acute pancreatitis (grade 5)
Cardiac arrhythmias (grade 5)
Cardiac arrhythmias (grade 5)
Other AEs:
Extravasation
Injection site ulceration
Injection site necrosis
Slough injection site
Sources:
AEs

AEs

AESignificanceDosePopulation
Cardiopulmonary arrest
1600 mg single, intravenous
Overdose
unhealthy, 17
n = 1
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Age Group: 17
Population Size: 1
Sources:
Hepatic impairment
1600 mg single, intravenous
Overdose
unhealthy, 17
n = 1
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Age Group: 17
Population Size: 1
Sources:
Hypotension
1600 mg single, intravenous
Overdose
unhealthy, 17
n = 1
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Age Group: 17
Population Size: 1
Sources:
Impaired renal function
1600 mg single, intravenous
Overdose
unhealthy, 17
n = 1
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Age Group: 17
Population Size: 1
Sources:
Acute pancreatitis Disc. AE
300 mg 1 times / month multiple, respiratory
Recommended
Dose: 300 mg, 1 times / month
Route: respiratory
Route: multiple
Dose: 300 mg, 1 times / month
Sources: Page: p.6
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources: Page: p.6
Extravasation
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Injection site necrosis
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Injection site ulceration
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Slough injection site
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Hypotension grade 3-5
Disc. AE
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Acute pancreatitis grade 5
Disc. AE
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Cardiac arrhythmias grade 5
Disc. AE
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Cardiac arrhythmias grade 5
Disc. AE
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Hypoglycemia grade 5
Disc. AE
4 mg/kg 1 times / day multiple, intramuscular
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Extravasation
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Injection site necrosis
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Injection site ulceration
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Slough injection site
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Hypotension grade 3-5
Disc. AE
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Acute pancreatitis grade 5
Disc. AE
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Cardiac arrhythmias grade 5
Disc. AE
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Cardiac arrhythmias grade 5
Disc. AE
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Hypoglycemia grade 5
Disc. AE
4 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 4 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 4 mg/kg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Pneumonia due to Pneumocystis carinii
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 0.097 uM]
yes
Drug as victim
PubMed

PubMed

TitleDatePubMed
[Kidney failure during treatment of T. rhodesiense trypanosomiasis with pentamidin].
1977
Visceral leishmaniasis unresponsive to antimonial drugs. II. Response to high dosage sodium stibogluconate or prolonged treatment with pentamidine.
1985
Pentamidine treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Association with acute renal failure and myoglobinuria.
1985 Dec
Extrapyramidal symptoms in AIDS patients given low-dose metoclopramide or chlorpromazine.
1985 Nov 23
Pentamidine-associated hypotension and route of administration.
1985 Sep
Pentamidine and renal toxicity.
1985 Sep 12
Aggressive psychosis in AIDS patient on high-dose steroids.
1987 Sep 26
Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective, noncrossover study.
1988 Aug 15
Risk factors for hypoglycemia associated with pentamidine therapy for Pneumocystis pneumonia.
1988 Jul 15
Torsades de pointes during intravenous pentamidine isethionate therapy.
1989 Jan 15
Acute renal failure after nebulised pentamidine.
1989 Jun 3
Renal insufficiency with nebulised pentamidine.
1989 Oct 28
Structure-activity relationships of analogs of pentamidine against Plasmodium falciparum and Leishmania mexicana amazonensis.
1990 Jul
Novel pentamidine analogs in the treatment of experimental Pneumocystis carinii pneumonia.
1990 Jun
Reye's syndrome in adult with AIDS.
1990 Jun 16
Pentamidine-induced facial numbness.
1991 Apr
[Transitory acute kidney insufficiency and insulin-dependent after treatment of kala-azar with pentamidine and N-methylglucamine antimony].
1991 May
Pentamidine-associated nephrotoxicity and hyperkalemia in patients with AIDS.
1991 Nov
Anti-cryptosporidial drug activity screened with an immunosuppressed rat model.
1991 Nov-Dec
Cardiac arrest during treatment of Pneumocystis carinii pneumonia with intravenous pentamidine isethionate.
1992
High pentamidine levels associated with hypoglycemia and azotemia in a patient with Pneumocystis carinii pneumonia.
1992 Aug
Hematuria associated with pentamidine therapy for Pneumocystis carinii pneumonia.
1992 Jun
Torsade de pointes after inhaled pentamidine.
1992 Nov
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.
1992 Sep
Antileishmanial drugs cause up-regulation of interferon-gamma receptor 1, not only in the monocytes of visceral leishmaniasis cases but also in cultured THP1 cells.
2003 Apr
New agents active against Mycobacterium avium complex selected by molecular topology: a virtual screening method.
2004 Jan
Novel bisbenzamidines as potential drug candidates for the treatment of Pneumocystis carinii pneumonia.
2004 Sep 6
Search of chemical scaffolds for novel antituberculosis agents.
2005 Apr
A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system.
2005 Feb
Pentamidine-induced long QT syndrome and block of hERG trafficking.
2005 Jan
Detection of immunotoxicity using T-cell based cytokine reporter cell lines ("Cell Chip").
2005 Jan 15
Protein trafficking abnormalities: a new mechanism in drug-induced long QT syndrome.
2005 May
Pentamidine is an antiparasitic and apoptotic drug that selectively modifies ubiquitin.
2005 Oct
Use of Leishmania donovani field isolates expressing the luciferase reporter gene in in vitro drug screening.
2005 Sep
[Cutaneous leishmaniasis--an import from Belize].
2007
Cellulose biosynthesis pathway is a potential target in the improved treatment of Acanthamoeba keratitis.
2007 May
Using the zebrafish lateral line to screen for ototoxicity.
2008 Jun
Pentamidine dosage: a base/salt confusion.
2008 May 28
Synthesis and antiprotozoal activity of cationic 2-phenylbenzofurans.
2008 Nov 13
Effects of acute intravenous administration of pentamidine, a typical hERG-trafficking inhibitor, on the cardiac repolarization process of halothane-anesthetized dogs.
2009 Aug
Synthesis and antiprotozoal activity of pyridyl analogues of pentamidine.
2009 Aug 13
Two cases of visceral leishmaniasis in Colombia resistant to meglumine antimonial treatment.
2009 Jul-Aug
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.
2010 Dec
Bisbenzamidine derivative, pentamidine represses DNA damage response through inhibition of histone H2A acetylation.
2010 Feb 9
Bisbenzamidines as antifungal agents. are both amidine functions required to observe an anti-Pneumocystis carinii activity?
2010 Jun 11
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
The pharmacological profile of brain liver intestine Na+ channel: inhibition by diarylamidines and activation by fenamates.
2011 Nov
Synthetic chromanol derivatives and their interaction with complex III in mitochondria from bovine, yeast, and Leishmania.
2011 Oct 17
Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.
2013 Dec
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: 300 mg once every four weeks administered via the Respirgard
The recommended adult dosage is 300 mg once every four weeks administered via the Respirgard® II nebulizer. The dose should be delivered until the nebulizer chamber is empty (approximately 30 to 45 minutes). The flow rate should be 5 to 7 liters per minute from a 40 to 50 pounds per square inch (PSI) air or oxygen source. Alternatively, a 40 to 50 PSI air compressor can be used with flow limited by setting the flowmeter at 5 to 7 liters per minute or by setting the pressure at 22 to 25 PSI. Low pressure (less than 20 PSI) compressors should not be used.
Route of Administration: Irrigation
In Vitro Use Guide
Pentamidine was found to be active against T. whipplei strains both in axenic medium and in cell culture, with minimum inhibitory concentration ranges of 0.125-0.25mg/L.
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:06:57 UTC 2021
Edited
by admin
on Sat Jun 26 09:06:57 UTC 2021
Record UNII
HMB3ISP7OB
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PENTAMIDINE MONOMESYLATE
Common Name English
PENTAMIDINE MONOMESILATE
Common Name English
BENZENECARBOXIMIDAMIDE, 4,4'-(1,5-PENTANEDIYLBIS(OXY))BIS-, MONOMETHANESULFONATE
Systematic Name English
PENTAMIDINE MONOMETHANESULFONATE
Common Name English
Code System Code Type Description
FDA UNII
HMB3ISP7OB
Created by admin on Sat Jun 26 09:06:57 UTC 2021 , Edited by admin on Sat Jun 26 09:06:57 UTC 2021
PRIMARY
CAS
112667-20-6
Created by admin on Sat Jun 26 09:06:57 UTC 2021 , Edited by admin on Sat Jun 26 09:06:57 UTC 2021
PRIMARY
PUBCHEM
24834404
Created by admin on Sat Jun 26 09:06:57 UTC 2021 , Edited by admin on Sat Jun 26 09:06:57 UTC 2021
PRIMARY
EPA CompTox
112667-20-6
Created by admin on Sat Jun 26 09:06:57 UTC 2021 , Edited by admin on Sat Jun 26 09:06:57 UTC 2021
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY