A population pharmacokinetic study to accelerate early phase clinical development for a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus.

In order to optimize teriflunomide sodium (TERS) dose regimen for phase II study, a population pharmacokinetic (Pop PK) model integrated enterohepatic circulation (EHC) mechanism was developed using PK data after single oral administration of TERS and leflunomide (LEF) in healthy volunteers (HV). Weight and sex were identified to affect the distribution volume of central compartment. The impacts of ABCG2 34G>A gene polymorphism on absorption and clearance was found for the first time. Model informed TERS dosage design optimization based on a translational study on LEF PK profiles in healthy subjects and rheumatoid arthritis (RA) patients. Loading dose (LD) of 100 mg for 3 days and maintained 15 mg/day was recommended for phase II study after balancing the efficacy and safety.Unlabelled Image