Pharmacokinetic interaction between rifampicin and the once-daily combination of saquinavir and low-dose ritonavir in HIV-infected patients with tuberculosis
| Autor: | Paquita Sánchez, Imma Ocaña, Leonor Pou, Pere Domingo, Manuel Crespo, Carlos Azuaje, Josep Lluis Lopez-Colomes, Vicenç Falcó, Esteban Ribera, Maria A. Sambeat, Rosa M Lopez, Joan Colomer, Maria Feijoo, Adria Curran, Albert Pahissa |
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| Rok vydání: | 2007 |
| Předmět: |
Microbiology (medical)
Adult Male Anti-HIV Agents viruses Antitubercular Agents HIV Infections Pharmacology medicine Humans Tuberculosis Pharmacology (medical) Drug Interactions Didanosine Ethambutol Chromatography High Pressure Liquid Saquinavir Antibacterial agent Models Statistical Ritonavir business.industry Isoniazid HIV Protease Inhibitors biochemical phenomena metabolism and nutrition Pyrazinamide bacterial infections and mycoses Infectious Diseases Area Under Curve Female Spectrophotometry Ultraviolet Rifampin business Rifampicin medicine.drug |
| Zdroj: | The Journal of antimicrobial chemotherapy. 59(4) |
| ISSN: | 0305-7453 |
| Popis: | Objectives To assess plasma steady-state pharmacokinetics (PK) of rifampicin, isoniazid, saquinavir and ritonavir in HIV and tuberculosis (TB) co-infected patients, and investigate potential interactions between TB drugs and protease inhibitors (PIs). Methods Open-label, single-arm, sequential PK study including 22 patients with HIV infection and TB. During the first 2 months, patients received rifampicin, isoniazid and pyrazinamide, with or without ethambutol (first PK study, n = 22). Then patients stopped pyrazinamide and ethambutol and started once-daily antiretroviral therapy (ART) with didanosine, lamivudine, ritonavir (200 mg) and saquinavir (1600 mg) (second PK study, n = 18). Patients stopped all TB drugs after 9 months continuing the same ART (third PK study, n = 15). Differences between TB drug parameters in the first and second PK studies, and between PI parameters in the second and third PK studies were used to assess interactions. Results Rifampicin and isoniazid pharmacokinetics did not change substantially with saquinavir and ritonavir. A significant 39.5%, 34.9% and 48.7% reduction in median saquinavir AUC(0-24), C(max) and C(trough), respectively, was seen with rifampicin and isoniazid. Ritonavir AUC(0-24), C(max) and C(trough) decreased 42.5%, 49.6% and 64.3%, respectively, with rifampicin and isoniazid. Conclusions There was a significant interaction between saquinavir, ritonavir and rifampicin, with reduction in median plasma concentrations of saquinavir and ritonavir. Saquinavir should be given with caution in patients receiving rifampicin. Twice-daily dosing or higher saquinavir doses in once-daily administration should be tested to obtain more appropriate plasma levels. |
| Databáze: | OpenAIRE |
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