Pharmacokinetic characterization of different dose combinations of coadministered tipranavir and ritonavir in healthy volunteers.

Abstract:

PURPOSE:To characterize the steady-state pharmacokinetic combination of the nonpeptidic protease inhibitor tipranavir (TPV) with ritonavir (RTV) in 95 healthy adult volunteers, a phase 1, single-center, open-label, randomized, parallel-group trial was conducted. METHOD:Participants received 250-mg self-emulsifying drug delivery system (SEDDS) capsules of TPV at doses between 250 mg and 1250 mg twice daily for 11 days, then received one or two RTV 100-mg SEDDS capsules, in addition to the TPV capsules, for the next 21 days. RESULTS:Coadministration of TPV and RTV (TPV/r) resulted in a greater than 20-fold increase in steady-state TPV trough concentrations (Cssmin) as compared with TPV at steady state alone. Mean TPV Cssmin was above a preliminary target threshold of 20 microM with all but one of the RTV-boosted doses; without boosting, none of the TPV-alone doses exceeded the threshold. The average steady-state Cssmin for TPV 500 mg and 750 mg with RTV 100 mg or 200 mg were 20 to 57 times the protein-adjusted TPV IC90R49\CCR418569) for protease inhibitor-resistant HIV-1. An erythromycin breath test, a surrogate marker for cytochrome P450 isoenzyme 3A4 activity, indicated that all TPV/r combinations given provided net inhibition of this isoenzyme. The most frequent treatment-related adverse events were mild gastrointestinal symptoms. CONCLUSION:This phase 1 study demonstrated that RTV-boosted TPV achieves concentrations that are expected to be effective in treating drug-experienced patients.

journal_name

HIV Clin Trials

journal_title

HIV clinical trials

authors

MacGregor TR,Sabo JP,Norris SH,Johnson P,Galitz L,McCallister S

doi

10.1310/RRX7-49ME-27V7-MWWV

keywords:

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

371-82

issue

6

eissn

1528-4336

issn

1945-5771

journal_volume

5

pub_type

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    pub_type: 杂志文章,meta分析

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