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- Title
Lack of a pharmacokinetic interaction between steady-state tipranavir/ritonavir and single-dose valacyclovir in healthy volunteers.
- Authors
Sabo, John; Cong, Xiuyu (Julie); Kraft, Michael-Friedrich; Wallace, Lacey; Castles, Mark; Mauss, Stefan; MacGregor, Thomas
- Abstract
Objective: This study assessed the single-dose pharmacokinetics of the herpes antiviral acyclovir (administered as the pro-drug valacyclovir) alone and in combination with twice-daily 200 mg ritonavir-boosted tipranavir (500 mg) at steady state. Methods: The study was an open label, one-sequence cross-over pharmacokinetic study in HIV-negative adults. Plasma drug concentrations were measured by validated LC/MS/MS assays; pharmacokinetics (AUC, C) were determined using noncompartmental methods. The geometric mean ratio and 90% confidence interval [GMR, 90% CI] were used to evaluate the drug interaction. Results: Twenty-six of 29 subjects completed the trial. With steady-state tipranavir/ritonavir, acyclovir C decreased 4.9% [0.95, 0.88-1.02] and AUC increased 6.6% [1.07, 1.04-1.09]. The majority of subjects experienced at least one adverse event, most of which were mild gastrointestinal disorders. Three subjects discontinued tipranavir/ritonavir treatment as a result of drug-related increases in ALT/AST, including one subject who experienced mild upper abdominal pain. All subjects recovered without sequelae. Conclusions: When administered as a single dose of valacyclovir with steady-state tipranavir/ritonavir, there were no clinically important changes in acyclovir pharmacokinetics. This result indicates that valacyclovir can be co-administered safely with no dose adjustments.
- Subjects
ACYCLOVIR; ANALYSIS of variance; ANTIVIRAL agents; COMBINATION drug therapy; CONFIDENCE intervals; CROSSOVER trials; DRUG interactions; HIV infections; LIVER function tests; ORAL drug administration; PRODRUGS; WHITE people; PROTEASE inhibitors; TIPRANAVIR (Drug); DRUG dosage
- Publication
European Journal of Clinical Pharmacology, 2011, Vol 67, Issue 3, p277
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-010-0907-1