Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in HIV-infected Indian children

SETTING: Co-infection with the human immunodeficiency virus (HIV) may lead to inadequate plasma concentrations of anti-tuberculosis drugs in children with tuberculosis (TB).OBJECTIVE: To describe the influence of HIV infection on the pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in children.DESIGN: Prospective drug estimation study in two cohorts of children: HIV-infected (n = 24) and non-HIV-infected (n = 32) with TB. Dosages used were based on earlier World Health Organization recommendations. All four drugs were estimated simultaneously using liquid chromatography mass spectrometry.RESULTS: The HIV-TB co-infected children had a mean age of 105.9 months (standard deviation 43.1); there were 10 girls (41.7%). The maximum plasma concentration (Cmax), time taken to achieve Cmax, area under curve from 0-4 h and 2 h concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) were not affected by the HIV status of the children. Ethambutol (EMB) concentrations were lower in HIV-TB co-infected children. Inadequate 2 h concentrations of INH, RMP and EMB were found in the majority of the children in both groups. PZA concentrations were adequate in almost all children. Younger age and lower dose were associated with lower 2 h concentrations of INH and RMP.CONCLUSION: Inadequate concentrations of INH, RMP and EMB in both HIV-TB-infected and non-HIV-infected children provide support for the recently revised recommended doses of INH and RMP. EMB levels were lower in HIV-infected children; however, more studies are needed to validate this observation.