An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors.
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Goh BC, Reddy NJ, Dandamudi UB, Laubscher KH, Peckham T, Hodge JP, Suttle AB, Arumugham T, Xu Y, Xu CF, Lager J, Dar MM, Lewis LD
An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors.
Clin Pharmacol Ther. 2010 Nov;88(5):652-9. doi: 10.1038/clpt.2010.158. Epub 2010 Sep 29.
- PubMed ID
- 20881954 [ View in PubMed]
- Abstract
Pazopanib, an oral inhibitor of vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-kit kinases, inhibits multiple cytochrome P450 (CYP450) enzymes in vitro. This study in patients with advanced cancer evaluated the effect of pazopanib on CYP450 function by comparing the pharmacokinetics of CYP-specific probe drugs in the presence and absence of pazopanib. The probes used included midazolam (CYP3A specific), warfarin (CYP2C9 specific), omeprazole (CYP2C19 specific), caffeine (CYP1A2 specific), and dextromethorphan (CYP2D6 specific). The estimated ratios of the geometric means (90% confidence interval (CI)) for the area under the curve to the last measurable point (AUC(0-t)) for these probe drugs with/without pazopanib were as follows: midazolam, 1.35 (1.18-1.54); omeprazole, 0.81 (0.59-1.12); caffeine, 1.00 (0.77-1.30); and S-warfarin, 0.93 (0.84-1.03). The geometric least-squares (LS) mean ratio of urine dextromethorphan:dextrorphan ranged from 1.33 (0-4-h interval) to 1.64 (4-8-h interval). The data suggest that pazopanib is a weak inhibitor of CYP3A4 and CYP2D6 and has no effect on CYP1A2, CYP2C9, and CYP2C19 in patients with advanced cancer.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Pazopanib Cytochrome P450 2D6 Protein Humans UnknownInhibitorDetails Pazopanib Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwarePazopanibMethimazole The metabolism of Pazopanib can be decreased when combined with Methimazole. PazopanibVoriconazole The metabolism of Pazopanib can be decreased when combined with Voriconazole. PazopanibEfavirenz The metabolism of Pazopanib can be decreased when combined with Efavirenz. PazopanibDelavirdine The metabolism of Pazopanib can be decreased when combined with Delavirdine. PazopanibTelithromycin The metabolism of Pazopanib can be decreased when combined with Telithromycin.