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Darunavir: pharmacokinetics and drug interactions
David Back1, Vanitha Sekar, Richard M W Hoetelmans
1Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK. daveback@liverpool.ac.uk
Antiviral Therapy
|April 9, 2008
Summary
Darunavir, an HIV protease inhibitor, effectively treats HIV, including resistant strains. When combined with ritonavir, drug interactions are manageable, simplifying co-administration with other medications.
Area of Science:
- Pharmacology
- Virology
- Drug Metabolism
Background:
- Darunavir (TMC114) is a potent HIV protease inhibitor with activity against wild-type and multidrug-resistant HIV-1.
- Darunavir is metabolized by cytochrome P450 3A (CYP3A) and coadministered with ritonavir to enhance its plasma concentrations and allow lower daily dosing.
- Ritonavir inhibits CYP3A, increasing darunavir's terminal elimination half-life (t1/2) to 15 hours.
Purpose of the Study:
- To review pharmacokinetic and drug-drug interaction studies of darunavir/ritonavir (darunavir/r).
- To provide guidance on co-administering darunavir/r with other antiretroviral and non-antiretroviral medications.
- To characterize the manageability of drug interactions involving darunavir/r.
Main Methods:
- Pharmacokinetic studies in healthy volunteers and HIV-infected patients.
- Drug-drug interaction assessments across various therapeutic areas.
- Review of published and unpublished data on darunavir/r interactions.
Main Results:
- Darunavir/r interactions are well-characterized and generally manageable.
- For most co-administered drugs, no dose adjustments for darunavir/r or the interacting drug are necessary.
- The pharmacokinetic profile of darunavir is significantly influenced by ritonavir boosting.
Conclusions:
- Darunavir/r can be safely co-administered with a wide range of medications.
- Understanding drug interactions is crucial for optimizing HIV therapy with darunavir/r.
- The extensive interaction program supports the clinical use of darunavir/r in diverse patient populations.
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