Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C19H28O8 |
Molecular Weight | 384.4208 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 8 / 8 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC[C@@H](C)[C@]3([H])CC[C@@]4(C)OO[C@@]13[C@]([H])(O[C@@H](OC(=O)CCC(O)=O)[C@@H]2C)O4
InChI
InChIKey=FIHJKUPKCHIPAT-AHIGJZGOSA-N
InChI=1S/C19H28O8/c1-10-4-5-13-11(2)16(23-15(22)7-6-14(20)21)24-17-19(13)12(10)8-9-18(3,25-17)26-27-19/h10-13,16-17H,4-9H2,1-3H3,(H,20,21)/t10-,11-,12+,13+,16-,17-,18-,19-/m1/s1
Molecular Formula | C19H28O8 |
Molecular Weight | 384.4208 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 8 / 8 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/11231359 | https://www.ncbi.nlm.nih.gov/pubmed/9241384 | https://www.ncbi.nlm.nih.gov/pubmed/1966574https://www.cdc.gov/malaria/diagnosis_treatment/artesunate.htmlhttp://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001199/WC500118113.pdfCurator's Comment: Description was created based on several sources, including
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001199/human_med_001450.jsp&mid=WC0b01ac058001d124 | https://www.hpra.ie/docs/default-source/3rd-party-documents/educational-materials/eurartesim_hcp-guide.pdf?sfvrsn=4 | https://www.ncbi.nlm.nih.gov/pubmed/20649950
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11231359 | https://www.ncbi.nlm.nih.gov/pubmed/9241384 | https://www.ncbi.nlm.nih.gov/pubmed/1966574https://www.cdc.gov/malaria/diagnosis_treatment/artesunate.htmlhttp://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001199/WC500118113.pdf
Curator's Comment: Description was created based on several sources, including
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001199/human_med_001450.jsp&mid=WC0b01ac058001d124 | https://www.hpra.ie/docs/default-source/3rd-party-documents/educational-materials/eurartesim_hcp-guide.pdf?sfvrsn=4 | https://www.ncbi.nlm.nih.gov/pubmed/20649950
Artenimol (dihydroartemisinin) is a derivate of antimalarial compound artemisinin. Artenimol (dihydroartemisinin) is able to reach high concentrations within the parasitized erythrocytes. Its endoperoxide bridge is thought to be essential for its antimalarial activity, causing free-radical damage to parasite membrane systems including:
• Inhibition of falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase, • Interference with mitochondrial electron transport • Interference with parasite transport proteins • Disruption of parasite mitochondrial function. Dihydroartemisinin in combination with piperaquine tetraphosphate (Eurartesim, EMA-approved in 2011) is indicated for the treatment of uncomplicated Plasmodium falciparum malaria. The formulation meets WHO recommendations, which advise combination treatment for Plasmodium falciparum malaria to reduce the risk of resistance development, with artemisinin-based preparations regarded as the ‘policy standard’. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC148951/https://www.ncbi.nlm.nih.gov/pubmed/12499215
Curator's Comment: Active metabolite of artesunate was detected in CSF after intravenous administration of artesunate.
Originator
Sources: Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan (1982), 2, (2), 99-103.https://www.ncbi.nlm.nih.gov/pubmed/8891104http://adisinsight.springer.com/drugs/800023198
Curator's Comment: Indicated originators are originators of Dihydroartemisinin/piperaquine formulation. Originator of Dihydroartemisinin is unknown.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL613064 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11802960 |
|||
Target ID: P06685 Gene ID: 24211.0 Gene Symbol: Atp1a1 Target Organism: Rattus norvegicus (Rat) |
|||
Target ID: CHEMBL364 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1394893 |
4.1 nM [IC50] | ||
Target ID: CHEMBL612889 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1307277 |
|||
Target ID: CHEMBL612653 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3009719 |
|||
Target ID: CHEMBL364 |
|||
Target ID: CHEMBL2311221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25348537 |
|||
Target ID: CHEMBL2366043 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25348537 |
|||
Target ID: CHEMBL364 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8891104 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Sodium artesunate Approved UsePlasmodium falciparum malaria |
|||
Curative | Eurartesim Approved UseEurartesim tablets (piperaquine tetraphosphate in combination with dihydroartemisinin) are indicated for the treatment of uncomplicated Plasmodium falciparum malaria in adults, children and infants aged ≥6 months and weighing ≥5kg. Launch Date1.31958715E12 |
|||
Curative | Unknown Approved UseAlthough not FDA-approved for use in the United States, artesunate is used as the treatment of choice for severe malaria by the World Health Organization (WHO) over quinidine. |
|||
Curative | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.1 μg/mL |
2.4 mg/kg multiple, intravenous dose: 2.4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
ARTENIMOL unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
3.3 μg/mL |
2.4 mg/kg multiple, intravenous dose: 2.4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
ARTESUNATE unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.5 μg × h/mL |
2.4 mg/kg multiple, intravenous dose: 2.4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
ARTENIMOL unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
0.7 μg × h/mL |
2.4 mg/kg multiple, intravenous dose: 2.4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
ARTESUNATE unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.3 h |
2.4 mg/kg multiple, intravenous dose: 2.4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
ARTENIMOL unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
0.3 h |
2.4 mg/kg multiple, intravenous dose: 2.4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
ARTESUNATE unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7% |
2.4 mg/kg multiple, intravenous dose: 2.4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
ARTENIMOL unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
7% |
2.4 mg/kg multiple, intravenous dose: 2.4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
ARTESUNATE unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Other AEs: Anemia, Transaminases increased... Other AEs: Anemia (65%) Sources: Transaminases increased (27%) Thrombocytopenia (18%) Hyperbilirubinemia (14%) Acute renal failure (10%) Leukocytosis (10%) Acute respiratory distress syndrome (8%) Lymphopenia (7%) Neutropenia (5%) Disseminated intravascular coagulation (3%) Creatinine increased (3%) Pneumonia (3%) Pulmonary edema (3%) Diarrhea (3%) |
100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
unhealthy, 15-35 years n = 31 Health Status: unhealthy Condition: Uncomplicated Malaria Age Group: 15-35 years Sex: M Population Size: 31 Sources: |
Other AEs: Nausea, Dizziness... Other AEs: Nausea (grade 1, 45%) Sources: Dizziness (grade 1, 52%) Vomiting (grade 1, 26%) Convulsions (grade 1, 3%) Bradycardia (grade 1, 23%) |
2.4 mg/kg 1 times / day multiple, intravenous|oral (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous|oral Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 2-87 years n = 730 Health Status: unhealthy Condition: malaria Age Group: 2-87 years Sex: M+F Population Size: 730 Sources: |
Other AEs: Acute renal failure, Hemoglobinuria... Other AEs: Acute renal failure (8.9%) Sources: Hemoglobinuria (6.7%) Jaundice (2.3%) |
25 mg/kg 2 times / 3 weeks multiple, intravenous Highest studied dose Dose: 25 mg/kg, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/kg, 2 times / 3 weeks Sources: |
unhealthy, 58 years n = 2 Health Status: unhealthy Condition: advanced solid tumor malignancies Age Group: 58 years Sex: M+F Population Size: 2 Sources: |
DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3, 1 patient) Sources: Vomiting (grade 3, 1 patient) ALT increased (grade 3-4, 1 patient) Neutropenic infection (grade 3-4, 1 patient) |
18 mg/kg 2 times / 3 weeks multiple, intravenous MTD Dose: 18 mg/kg, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 18 mg/kg, 2 times / 3 weeks Sources: |
unhealthy, 58 years n = 6 Health Status: unhealthy Condition: advanced solid tumor malignancies Age Group: 58 years Sex: M+F Population Size: 6 Sources: |
DLT: Hypersensitivity reaction... Dose limiting toxicities: Hypersensitivity reaction (grade 3, 1 patient) Sources: |
12 mg/kg 2 times / 3 weeks multiple, intravenous Studied dose Dose: 12 mg/kg, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 12 mg/kg, 2 times / 3 weeks Sources: |
unhealthy, 58 years n = 6 Health Status: unhealthy Condition: advanced solid tumor malignancies Age Group: 58 years Sex: M+F Population Size: 6 Sources: |
DLT: Neutropenic fever... Dose limiting toxicities: Neutropenic fever (grade 3, 1 patient) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Acute renal failure | 10% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Leukocytosis | 10% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Hyperbilirubinemia | 14% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Thrombocytopenia | 18% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Transaminases increased | 27% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Creatinine increased | 3% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Diarrhea | 3% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Disseminated intravascular coagulation | 3% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Pneumonia | 3% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Pulmonary edema | 3% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Neutropenia | 5% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Anemia | 65% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Lymphopenia | 7% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Acute respiratory distress syndrome | 8% | 2.4 mg/kg 1 times / day multiple, intravenous (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 1-72 years n = 92 Health Status: unhealthy Condition: malaria Age Group: 1-72 years Sex: M+F Population Size: 92 Sources: |
Bradycardia | grade 1, 23% | 100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
unhealthy, 15-35 years n = 31 Health Status: unhealthy Condition: Uncomplicated Malaria Age Group: 15-35 years Sex: M Population Size: 31 Sources: |
Vomiting | grade 1, 26% | 100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
unhealthy, 15-35 years n = 31 Health Status: unhealthy Condition: Uncomplicated Malaria Age Group: 15-35 years Sex: M Population Size: 31 Sources: |
Convulsions | grade 1, 3% | 100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
unhealthy, 15-35 years n = 31 Health Status: unhealthy Condition: Uncomplicated Malaria Age Group: 15-35 years Sex: M Population Size: 31 Sources: |
Nausea | grade 1, 45% | 100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
unhealthy, 15-35 years n = 31 Health Status: unhealthy Condition: Uncomplicated Malaria Age Group: 15-35 years Sex: M Population Size: 31 Sources: |
Dizziness | grade 1, 52% | 100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: |
unhealthy, 15-35 years n = 31 Health Status: unhealthy Condition: Uncomplicated Malaria Age Group: 15-35 years Sex: M Population Size: 31 Sources: |
Jaundice | 2.3% | 2.4 mg/kg 1 times / day multiple, intravenous|oral (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous|oral Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 2-87 years n = 730 Health Status: unhealthy Condition: malaria Age Group: 2-87 years Sex: M+F Population Size: 730 Sources: |
Hemoglobinuria | 6.7% | 2.4 mg/kg 1 times / day multiple, intravenous|oral (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous|oral Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 2-87 years n = 730 Health Status: unhealthy Condition: malaria Age Group: 2-87 years Sex: M+F Population Size: 730 Sources: |
Acute renal failure | 8.9% | 2.4 mg/kg 1 times / day multiple, intravenous|oral (complex) Recommended Dose: 2.4 mg/kg, 1 times / day Route: intravenous|oral Route: multiple Dose: 2.4 mg/kg, 1 times / day Sources: |
unhealthy, 2-87 years n = 730 Health Status: unhealthy Condition: malaria Age Group: 2-87 years Sex: M+F Population Size: 730 Sources: |
Nausea | grade 3, 1 patient DLT |
25 mg/kg 2 times / 3 weeks multiple, intravenous Highest studied dose Dose: 25 mg/kg, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/kg, 2 times / 3 weeks Sources: |
unhealthy, 58 years n = 2 Health Status: unhealthy Condition: advanced solid tumor malignancies Age Group: 58 years Sex: M+F Population Size: 2 Sources: |
Vomiting | grade 3, 1 patient DLT |
25 mg/kg 2 times / 3 weeks multiple, intravenous Highest studied dose Dose: 25 mg/kg, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/kg, 2 times / 3 weeks Sources: |
unhealthy, 58 years n = 2 Health Status: unhealthy Condition: advanced solid tumor malignancies Age Group: 58 years Sex: M+F Population Size: 2 Sources: |
ALT increased | grade 3-4, 1 patient DLT |
25 mg/kg 2 times / 3 weeks multiple, intravenous Highest studied dose Dose: 25 mg/kg, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/kg, 2 times / 3 weeks Sources: |
unhealthy, 58 years n = 2 Health Status: unhealthy Condition: advanced solid tumor malignancies Age Group: 58 years Sex: M+F Population Size: 2 Sources: |
Neutropenic infection | grade 3-4, 1 patient DLT |
25 mg/kg 2 times / 3 weeks multiple, intravenous Highest studied dose Dose: 25 mg/kg, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 25 mg/kg, 2 times / 3 weeks Sources: |
unhealthy, 58 years n = 2 Health Status: unhealthy Condition: advanced solid tumor malignancies Age Group: 58 years Sex: M+F Population Size: 2 Sources: |
Hypersensitivity reaction | grade 3, 1 patient DLT |
18 mg/kg 2 times / 3 weeks multiple, intravenous MTD Dose: 18 mg/kg, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 18 mg/kg, 2 times / 3 weeks Sources: |
unhealthy, 58 years n = 6 Health Status: unhealthy Condition: advanced solid tumor malignancies Age Group: 58 years Sex: M+F Population Size: 6 Sources: |
Neutropenic fever | grade 3, 1 patient DLT |
12 mg/kg 2 times / 3 weeks multiple, intravenous Studied dose Dose: 12 mg/kg, 2 times / 3 weeks Route: intravenous Route: multiple Dose: 12 mg/kg, 2 times / 3 weeks Sources: |
unhealthy, 58 years n = 6 Health Status: unhealthy Condition: advanced solid tumor malignancies Age Group: 58 years Sex: M+F Population Size: 6 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
weak [IC50 32.3 uM] | ||||
weak [IC50 75.4 uM] | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213036Orig1s000MultidisciplineR.pdf#page=258 Page: 258.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213036Orig1s000MultidisciplineR.pdf#page=258 Page: 258.0 |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Antimalarial agents, 2. Artesunate, an inhibitor of cytochrome oxidase activity in Plasmodium berghei. | 1986 Jan-Feb |
|
[Effects of sodium artesunate on electrical properties and Na+,K(+)-ATPase activities of mouse small intestine]. | 1990 Jul |
|
Monotherapy with sodium artesunate for uncomplicated falciparum malaria in Thailand: a comparison of 5- and 7-day regimens. | 1997 Sep 30 |
|
Effects of sodium artesunate, a new antimalarial drug, on renal function. | 2001 Mar |
|
Diuretic effect of sodium artesunate in patients with malaria. | 2002 Nov |
|
Artesunate and mefloquine given simultaneously for three days via a prepacked blister is equally effective and tolerated as a standard sequential treatment of uncomplicated acute Plasmodium falciparum malaria: randomized, double-blind study in Thailand. | 2002 Nov |
|
Penetration of dihydroartemisinin into cerebrospinal fluid after administration of intravenous artesunate in severe falciparum malaria. | 2003 Jan |
|
Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. | 2003 Sep |
|
Randomized control trial of quinine and artesunate in complicated malaria. | 2004 Apr |
|
Artesunate in the treatment of metastatic uveal melanoma--first experiences. | 2005 Dec |
|
Mechanistic perspectives for 1,2,4-trioxanes in anti-cancer therapy. | 2005 Feb-Apr |
|
Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate. | 2005 Jan-Feb |
|
Adding artesunate to sulphadoxine-pyrimethamine greatly improves the treatment efficacy in children with uncomplicated falciparum malaria on the coast of Benin, West Africa. | 2007 Dec 21 |
|
Treatment of experimental nephrotic syndrome with artesunate. | 2007 Jul-Aug |
|
Auditory assessment of patients with acute uncomplicated Plasmodium falciparum malaria treated with three-day mefloquine-artesunate on the north-western border of Thailand. | 2008 Nov 6 |
|
Combination treatment of malignant B cells using the anti-CD20 antibody rituximab and the anti-malarial artesunate. | 2009 Jul |
|
The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria. | 2009 Sep 2 |
|
Factors determining sensitivity or resistance of tumor cell lines towards artesunate. | 2010 Apr 15 |
|
In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. | 2010 May |
|
Artesunate-mefloquine combination therapy in acute Plasmodium falciparum malaria in young children: a field study regarding neurological and neuropsychiatric safety. | 2010 Oct 21 |
|
Artesunate induces apoptosis through caspase-dependent and -independent mitochondrial pathways in human myelodysplastic syndrome SKM-1 cells. | 2014 Aug 5 |
|
Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria. | 2014 Jan 20 |
|
Delayed anemia after treatment with injectable artesunate in the Democratic Republic of the Congo: a manageable issue. | 2014 Oct |
|
Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs. | 2015 Jun |
|
Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. | 2015 Oct 19 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12479546
Curator's Comment: Oral route is possible: One group of 45 patients received 400 mg of Sodium artesunate on the first day of treatment and then 200 mg daily for 4 days for a total of 1200 mg (group I: 5-day treatment). A second group of 46 patients received 400 mg of Sodium artesunate on the first day of treatment and then 200 mg daily for 6 days for a total of 1600 mg (group II: 7-day treatment). 5- or 7-day regimens of sodium artesunate with a total dose of 1200-1600 mg are effective and safe in treating falciparum malaria acquired in Thailand.
https://www.ncbi.nlm.nih.gov/pubmed/9241384
Falciparum malaria treatment: 4 intravenous 60-mg doses
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3009719
The activity of the cytochrome oxidase, which is located in the plasma and the nuclear and the food-vacuole-limiting membranes as well as in the mitochondria of the trophozoites of Plasmodium berghei, was inhibited completely by sodium artesunate, an antimalarial drug, in vitro at 1 mM
Substance Class |
Chemical
Created
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admin
on
Edited
Fri Dec 16 17:43:50 UTC 2022
by
admin
on
Fri Dec 16 17:43:50 UTC 2022
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Record UNII |
60W3249T9M
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Validated (UNII)
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
651218
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FDA ORPHAN DRUG |
598517
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FDA ORPHAN DRUG |
221206
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WHO-ATC |
P01BE03
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FDA ORPHAN DRUG |
693719
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WHO-ESSENTIAL MEDICINES LIST |
6.5.3.1 (ART/AMO)
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WHO-ATC |
P01BF03
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WHO-ATC |
P01BF02
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WHO-ESSENTIAL MEDICINES LIST |
6.5.3.1
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WHO-ATC |
P01BF04
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WHO-ATC |
P01BF06
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EU-Orphan Drug |
EU/3/15/1521
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FDA ORPHAN DRUG |
125599
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NCI_THESAURUS |
C277
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Code System | Code | Type | Description | ||
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247
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PRIMARY | |||
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Artesunate
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88495-63-0
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CHEMBL361497
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6459
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18346
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PRIMARY | RxNorm | ||
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DTXSID3042681
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DB09274
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M2078
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PRIMARY | Merck Index | ||
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60W3249T9M
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63918
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6917864
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60W3249T9M
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PRIMARY | |||
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C73005
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7458
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712571
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PP-05
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ARTESUNATE
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PRIMARY | Description: A fine, white crystalline powder. Solubility: Very slightly soluble in water; very soluble in dichloromethane R; freely soluble in ethanol (~750 g/l) TS and acetone R. Category: Antimalarial. Storage: Artesunate should be kept in a well-closed container or, if sterile, in a hermetically closed container. It should be protected from light. Labelling: The label states where applicable:? that the substance is free from bacterial endotoxins;? that the substance is sterile. Definition: Artesunate contains not less than 96.0% and not more than 102.0% of artesunate (C19H28O8) using Assay method A, and not less than 98.0% and not more than 102.0% of artesunate (C19H28O8) using Assay method B, both calculated with reference to the anhydrous substance. | ||
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C039726
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1042850
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SUB05576MIG
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ARTESUNATE
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Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR |
WEAK
IC50
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TARGET ORGANISM->INHIBITOR |
IC50
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TRANSPORTER -> SUBSTRATE |
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SALT/SOLVATE -> PARENT |
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TRANSPORTER -> SUBSTRATE |
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BINDER->LIGAND |
BINDING
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TRANSPORTER -> INHIBITOR |
WEAK
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Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PARENT |
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METABOLITE ACTIVE -> PRODRUG |
ratio of alpha to beta DIHYDROARTEMISININ is 3.5
PLASMA
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
In the chromatogram obtained with solution (1): the area of any peak corresponding to impurity B (artemisinin) is not greater than 0.5 times the area of the principal peak obtained with solution (4) (0.5%).
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IMPURITY -> PARENT |
In the chromatogram obtained with solution (1): the area of any peak corresponding to impurity C, when multiplied by a correction factor of 0.07, is not greater than 0.2 times the area of the principal peak obtained with solution (4) (0.2%)
the sum of the corrected area of any peak corresponding to impurity C and the areas of all other peaks, other than the principal peak, is not greater than twice the area of the principal peak obtained with solution (4) (2.0%).
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Related Record | Type | Details | ||
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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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INTRAVENOUS ADMINISTRATION |
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Biological Half-life | PHARMACOKINETIC |
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IN PATIENTS WITH SEVERE MALARIA |
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