Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment
| Autor: | N B, Bhatt, C, Barau, A, Amin, E, Baudin, B, Meggi, C, Silva, V, Furlan, B, Grinsztejn, A, Barrail-Tran, M, Bonnet, A M, Taburet, Christine, Rouzioux |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Cyclopropanes Male Efavirenz Nevirapine Cmax Antitubercular Agents HIV Infections Pharmacology chemistry.chemical_compound Young Adult Pharmacokinetics medicine Isoniazid Humans Tuberculosis Pharmacology (medical) Reverse-transcriptase inhibitor business.industry Coinfection Stavudine Lamivudine Middle Aged Benzoxazines Infectious Diseases Treatment Outcome chemistry Alkynes Reverse Transcriptase Inhibitors Female Rifampin business medicine.drug Half-Life |
| Zdroj: | Antimicrobial agents and chemotherapy. 58(6) |
| ISSN: | 1098-6596 |
| Popis: | This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4 + T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum ( C max ) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid C max and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.) |
| Databáze: | OpenAIRE |
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