The impact of patient characteristics on the pharmacokinetics of Rifampicin

Abstract

Introduction: Rifampicin is a critical component of tuberculosis (TB) treatment, often dosed based on body weight. However, variability in pharmacokinetics (PK) can impact therapeutic outcomes. Understanding factors such as body weight, age, and sex is essential for optimizing dosing strategies and improving patient care in TB management. Objective: This study aims to evaluate the effects of covariates such as body weight, lean body mass, age, sex, and HIV status on the pharmacokinetics of rifampicin in TB treatment. Methods: Nineteen TB patients in the intensive phase were enrolled, receiving weight-based rifampicin dosing for at least 14 days. Blood samples (5 mL) were collected 4-6 times daily and analyzed using HPLC-UV. Data were analyzed using software MONOLIXSUITER12023 which contain MONOLIX for population pharmacokinetics estimation and PK-analix for average results of 19 patients to determine the relationship between covariates and PK parameters. Results: A one-compartment model with linear elimination and zero-order absorption described the data best. The volume of distribution decreased from 55 to 37.2 L due to effects of food and age. Clearance showed no significant covariate dependency, with a total objective function value decrease from 323.31 to 308.5. Clearance (Cl=9.1 L/h) was highly correlated with volume of distribution (Vd=37.2 L). Inter-individual variability (IIV) in clearance was 36.3% (CV=37.5). PKanalix analysis indicated higher clearance in patients taking 2 and 4 tablets (300 mg, 600 mg) and aged under 55. Volume of distribution was larger in males, HIV-negative patients, those older than 55, and those weighing less than 40 kg or over 55 kg. Conclusion: Rifampicin clearance was not significantly affected by covariates at the population PK level, warranting further investigation with larger data samples to confirm these findings.