en
Scientific article
English

Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment

CollaboratorsCalmy, Alexandraorcid
Published inAntimicrobial agents and chemotherapy, vol. 58, no. 6, p. 3182-3190
Publication date2014-06
First online date2014-03-24
Abstract

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 (Cmax) 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 Cmax 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.).

eng
Keywords
  • Adult
  • Alkynes
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / pharmacokinetics
  • Antitubercular Agents / therapeutic use
  • Benzoxazines / adverse effects
  • Benzoxazines / therapeutic use
  • Coinfection
  • Cyclopropanes
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • Half-Life
  • Humans
  • Isoniazid / adverse effects
  • Isoniazid / pharmacokinetics
  • Isoniazid / therapeutic use
  • Male
  • Middle Aged
  • Nevirapine / adverse effects
  • Nevirapine / therapeutic use
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Rifampin / adverse effects
  • Rifampin / pharmacokinetics
  • Rifampin / therapeutic use
  • Treatment Outcome
  • Tuberculosis / complications
  • Tuberculosis / drug therapy
  • Young Adult
Research group
Citation (ISO format)
BHATT, N B et al. Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment. In: Antimicrobial agents and chemotherapy, 2014, vol. 58, n° 6, p. 3182–3190. doi: 10.1128/AAC.02379-13
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal0066-4804
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