Mechanisms of pharmacokinetic and pharmacodynamic drug interactions associated with ritonavir-enhanced tipranavir.
Article Details
- CitationCopy to clipboard
Vourvahis M, Kashuba AD
Mechanisms of pharmacokinetic and pharmacodynamic drug interactions associated with ritonavir-enhanced tipranavir.
Pharmacotherapy. 2007 Jun;27(6):888-909. doi: 10.1592/phco.27.6.888.
- PubMed ID
- 17542771 [ View in PubMed]
- Abstract
Tipranavir is a nonpeptidic protease inhibitor that has activity against human immunodeficiency virus strains resistant to multiple protease inhibitors. Tipranavir 500 mg is coadministered with ritonavir 200 mg. Tipranavir is metabolized by cytochrome P450 (CYP) 3A and, when combined with ritonavir in vitro, causes inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A in addition to induction of glucuronidase and the drug transporter P-glycoprotein. As a result, drug-drug interactions between tipranavir-ritonavir and other coadministered drugs are a concern. In addition to interactions with other antiretrovirals, tipranavir-ritonavir interactions with antifungals, antimycobacterials, oral contraceptives, statins, and antidiarrheals have been specifically evaluated. For other drugs such as antiarrhythmics, antihistamines, ergot derivatives, selective serotonin receptor agonists (or triptans), gastrointestinal motility agents, erectile dysfunction agents, and calcium channel blockers, interactions can be predicted based on studies with other ritonavir-boosted protease inhibitors and what is known about tipranavir-ritonavir CYP and P-glycoprotein utilization. The highly complex nature of drug interactions dictates that cautious prescribing should occur with narrow-therapeutic-index drugs that have not been specifically studied. Thus, the known interaction potential of tipranavir-ritonavir is reported, and in vitro and in vivo data are provided to assist clinicians in predicting interactions not yet studied. As more clinical interaction data are generated, better insight will be gained into the specific mechanisms of interactions with tipranavir-ritonavir.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Ritonavir Cytochrome P450 1A2 Protein Humans UnknownInducerDetails Tipranavir Cytochrome P450 2C19 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareDidanosineTipranavir The serum concentration of Didanosine can be decreased when it is combined with Tipranavir. TipranavirPhenytoin The serum concentration of Tipranavir can be decreased when it is combined with Phenytoin. TipranavirFosphenytoin The serum concentration of Tipranavir can be decreased when it is combined with Fosphenytoin.