Limited data address the impact of HIV co-infection on the pharmacokinetics of anti-tuberculosis drugs in Sub-Saharan Africa. 47 Malawian adults underwent rich pharmacokinetic sampling at 0-0.5-1-2-3-4-6-8 and 24 hours post-dose. 51% were male; mean age was 34 years. 65% were HIV-positive with a mean CD4 count of 268 cells/μL. Anti-tuberculosis drugs were administered as fixed-dose combinations (rifampicin150mg/isoniazid75mg/pyrazinamide400mg/ethambutol275mg) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampicin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analysed by non-compartmental methods and analysis of variance of log-transformed summary parameters. Pharmacokinetic parameters were: rifampicin Cmax 4.129 (2.474-5.596)μg/mL, AUC0-2 4 21.32 (13.57-28.60)μg/mL*h, half-life 2.45 (1.86-3.08)h; isoniazid Cmax 3.97 (2.979-4.544)μg/mL, AUC0-24 22.5 (14.75-34.59)μg/mL*h, half-life 3.93 (3.18-4.73)h.; pyrazinamide Cmax 34.21 (30.00-41.60)μg/mL, AUC0-24 386.6 (320.0-463.7)μg/mL*h, half-life 6.821 (5.71-8.042)h; ethambutol Cmax 2.278 (1.694-3.098)μg/mL, AUC0-24 20.41 (16.18-26.27)μg/mL*h, half-life 7.507 (6.517-8.696)h. Isoniazid PK data analysis suggested that around two-thirds were slow acetylators. Dose, weight and weight-adjusted dose were not significant predictors of PK exposure probably due to weight-banded dosing.

 

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