Pharmacokinetics of saquinavir hard-gel/ritonavir and atazanavir when combined once daily in HIV Type 1-infected individuals administered different atazanavir doses
| Autor: | Marta Boffito, Andrew F. Hill, Mark T. Nelson, Brian Gazzard, Graeme Moyle, David Back, Laura Dickinson, Carl Fletcher, Desmond Maitland, Anton Pozniak |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Pyridines Immunology Atazanavir Sulfate Human immunodeficiency virus (HIV) HIV Infections Pharmacology medicine.disease_cause Statistics Nonparametric Pharmacokinetics Virology medicine Humans Drug Interactions Saquinavir Ritonavir business.industry Bilirubin HIV Protease Inhibitors Middle Aged Atazanavir Drug Combinations Infectious Diseases HIV-1 Drug Therapy Combination Female Once daily business Oligopeptides medicine.drug |
| Zdroj: | AIDS research and human retroviruses. 22(8) |
| ISSN: | 0889-2229 |
| Popis: | The pharmacokinetics and short-term safety of atazanavir 150 and 200 mg, when coadministered with saquinavir/ritonavir 1600/100 mg once daily, were evaluated. On day 1, atazanavir 150 mg once daily, was added to saquinavir/ritonavir regimens and sampling was performed to evaluate saquinavir, ritonavir, and atazanavir pharmacokinetics (day 11). Atazanavir was increased to 200 mg and pharmacokinetic assessment repeated (day 30). Geometric mean ratios (GMR) and 95% confidence intervals (CI) were used to compare saquinavir, ritonavir, and atazanavir pharmacokinetic parameters in the present study and for 14 of the subjects treated with saquinavir/ritonavir 1600/100 mg once daily without and with atazanavir 300 mg who participated in a previous trial. Geometric mean (GM) saquinavir AUC0-24, Ctrough, and Cmax were 30,589 and 32,312 ng . h/ml, 166 and 182 ng/ml, and 4267 and 4261 ng/ml when coadministered with atazanavir 150 and 200 mg (n = 18). On days 11 and 30, saquinavir and atazanavir Ctrough remained100 ng/ml in 13/18, 14/18, 18/18, and 17/18 patients. Among the above mentioned 14 subjects, significant increases in saquinavir Ctrough (87%, 92%, 99%), Cmax (40%, 55%, 44%), and AUC0-24 (51%, 60%, 63%) were observed with atazanavir 300, 150, and 200 mg. Ritonavir AUC0-24 and Cmax were significantly increased with the addition of atazanavir 300 mg only. Atazanavir enhances saquinavir and ritonavir by a mechanism that requires elucidation. While saquinavir enhancement was apparently independent of atazanavir dose, atazanavir 300 mg produced an increase in ritonavir Cmax, which is not observed with lower atazanavir doses. Atazanavir-related hyperbilirubinemia was dose dependent. However, higher saquinavir and atazanavir exposure may be required to suppress HIV-resistant strain replication. |
| Databáze: | OpenAIRE |
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