BackgroundTeriflunomide sodium, a novel derivative of leflunomide, was developed to treat systemic lupus erythematosus.ObjectiveThe objectives of this trial were to study the safety, pharmacokinetics, and pharmacogenetics of teriflunomide sodium in healthy Chinese subjects in order to support its accelerated development.MethodsA clinical study was designed as a single-dose, randomized, parallel, open-label study. Healthy volunteers were randomly assigned to take teriflunomide sodium 10mg or leflunomide 10mg. Eligible healthy volunteers were monitored over a 98-day observation period. Blood and urine samples were collected and analyzed for teriflunomide and its metabolite concentrations, and ABCG2 and CYP2C9 genotypes were detected. The safety profile was also collected.ResultsAll adverse events were mild in intensity, and all subjects completed this trial without any other treatment. After a single administration of teriflunomide sodium and leflunomide, teriflunomide maximal concentrations were 1.320.341mg/L and 0.7180.169mg/L, and area under the concentration-time curve from time zero to infinity (AUC) was 423 +/- 229mg<bold>h</bold>/L and 303 +/- 159 mg<bold>h</bold>/L, respectively. Overall, teriflunomide AUC in ABCG2 34A/A mutants was 70.4% lower than in wild-type ABCG2 34G/G after administration of teriflunomide sodium. In addition, after administration of leflunomide, teriflunomide AUC in ABCG2 34A/A mutants was 30.0% lower than in subjects carrying ABCG2 34G/G.Conclusions Teriflunomide sodium was generally safe and well tolerated in healthy Chinese subjects. The relative bioavailability of teriflunomide between teriflunomide sodium and leflunomide after a single dose administration was approximately 150%. Additionally, ABCG2 34G>A was found to significantly affect teriflunomide pharmacokinetics, which suggested ABCG2 34G>A may be a significant influencing factor.Clinical Trial Registration This study was registered at the China National Medical Products Administration (http://www.nmpa.gov.cn; registration number 2014L01935), and also at the China platform for registry and publicity of drug clinical trials (http://www.chinadrugtrials.org.cn; registration number CTR20150314).