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Pharmacokinetic characterization of three doses of tipranavir boosted with ritonavir on highly active antiretroviral therapy in treatment-experienced HIV-1 patients.
- Source :
-
HIV clinical trials [HIV Clin Trials] 2010 Jan-Feb; Vol. 11 (1), pp. 28-38. - Publication Year :
- 2010
-
Abstract
- Purpose: This study characterized the pharmacokinetic effects, safety, and antiretroviral activity of three different doses of the nonpeptidic protease inhibitor tipranavir, in combination with ritonavir administered twice daily for 28 days, on a number of triple-combination regimens containing a nonnucleoside reverse transcriptase inhibitor (efavirenz or nevirapine) plus two nucleoside reverse transcriptase inhibitors (abacavir, didanosine, lamivudine, stavudine, and zidovudine) or a three nucleoside reverse transcriptase inhibitor combination (zidovudine, lamivudine, and abacavir).<br />Methods: The study enrolled 208 HIV-1-positive patients who had been on stable antiretroviral treatment for at least 12 weeks prior to study entry and had an HIV-1 RNA load of delta 20,000 copies/mL. The patients were randomized to receive one of three dose combinations of tipranavir and ritonavir (1250/100 mg, 750/100 mg, and 250/200 mg) in addition to their antiretroviral (ARV) regimen for the next 22 days. The effects of twice-daily tipranavir and ritonavir combinations on the steady-state pharmacokinetics of the antiretrovirals were assessed by comparing pharmacokinetic parameters at baseline and after 3 weeks of coadministration.<br />Results: No clinically relevant changes were observed in the Cmin, Cmax, or AUC parameters for nevirapine, efavirenz, lamivudine, stavudine, or didanosine, when coadministered with tipranavir and ritonavir at the dose combinations studied. All three dose combinations of tipranavir and ritonavir decreased the systemic exposure of abacavir (by 35% to 44%) and zidovudine (by 31% to 42%). Consistent with previous tipranavir studies, gastrointestinal adverse events were those most frequently observed. These reactions tended to be mild, with the majority being of Grade 1, and only 8 being of Grade 3 or 4 in intensity. Virologic response improved from 40.4% of participants at baseline with <50 copies/mL to 67.6% at Day 28 of study following addition of tipranavir and ritonavir.<br />Conclusions: Tipranavir coadministered with ritonavir has been demonstrated to be safe, effective, and pose little potential for clinically meaningful drug interactions when added to the highly active antiretroviral therapy regimens containing nevirapine, efavirenz, lamivudine, stavudine, or didanosine.
- Subjects :
- Adult
Anti-HIV Agents administration & dosage
Antiretroviral Therapy, Highly Active methods
Area Under Curve
CD4 Lymphocyte Count
Female
HIV Infections immunology
HIV Infections virology
Humans
Male
Pyridines administration & dosage
Pyrones administration & dosage
Ritonavir administration & dosage
Sulfonamides
Viral Load drug effects
Anti-HIV Agents pharmacokinetics
HIV Infections drug therapy
HIV-1
Pyridines pharmacokinetics
Pyrones pharmacokinetics
Ritonavir pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-4336
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- HIV clinical trials
- Publication Type :
- Academic Journal
- Accession number :
- 20400409
- Full Text :
- https://doi.org/10.1310/hct1101-28