Rifampicin concentrations throughout the entire treatment duration of active tuberculosis; impact of sex and body mass index.

Abstract

Objectives: Rifampicin is a crucial part of an effective tuberculosis (TB) treatment. It has complicated pharmacokinetics (PK) with auto-induction and nonlinearity. Our objectives were to examine rifampicin concentrations throughout the entire treatment duration in individuals with active TB and to determine correlations between rifampicin concentrations, sex at birth, and body mass index (BMI).

Methods: We measured concentrations at 2-3 h post-dose (C2h) in an attempt to capture peak concentrations of rifampicin at treatment weeks 2, 4, 8, and subsequently every fourth week throughout the treatment period in patients with active TB. Linear mixed modelling was performed to analyse correlations between rifampicin concentration, week of treatment, sex at birth, and BMI.

Results: Forty-two participants were included, resulting in a total of 230 rifampicin concentration measurements. The intra-individual concentrations varied substantially throughout treatment but there was no correlation between week of treatment and rifampicin concentration. The concentration levels were significantly lower in men than in women, median difference -4.3 µg/mL (P < 0.001), median dose 13 mg/kg. Over time, women had a trend of decreasing concentrations and men an increasing trend. Underweight patients had significantly lower concentrations than normal weight individuals, median difference -4.1 µg/mL (P = 0.002). Rifampicin concentrations were below the recommended level of 8 µg/mL in 35/206 measurements (17%). No relapses occurred during 6 months of follow-up.

Conclusions: We found no significant changes in rifampicin concentrations during TB treatment. Both sex and BMI were associated with rifampicin concentrations.