In silico prediction of efavirenz and rifampicin drug-drug interaction considering weight and CYP2B6 phenotype

摘要: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Rifampicin is known to reduce the exposure of efavirenz. Despite lack adequate clinical support, most guidelines recommend an increased efavirenz dose in patients treated with both drugs, although some propose increase only weighing over 50 kg. WHAT STUDY ADDS • An example utilization vitro data predict vivo consequences metabolic drug–drug interactions, suggesting answers specific questions difficult study patients. Here efavirenz–rifampicin interaction was simulated question whether or not based on bodyweight. • The results from this simulation suggest that increasing may be appropriate bodyweights 50 kg. AIMS This aimed test a pharmacokinetic model could extrapolate nonclinical drug human after single and continuous dosing as well effects concomitant rifampicin further evaluate weight-based dosage recommendations used counteract rifampicin–efavirenz interaction. METHODS Efavirenz pharmacokinetics were using physiologically implemented Simcyp™ population-based simulator. Physicochemical metabolism obtained literature input for prediction parameters. The simulate 400 virtual patients, taking into account bodyweight CYP2B6 phenotype. RESULTS Apart absorption phase, predicted concentration–time profiles reasonably well, close agreement data. co-administration treatment showed minor decrease 16% (95% confidence interval 13–19) area under curve, same magnitude what has been clinically observed (22%). depended phenotype bodyweight. Increasing during successful 50 kg regardless status. CONCLUSIONS Our findings, approach limited data, support current cut-off increment when co-treating rifampicin.