A Single Dose of Baicalin Has No Clinically Significant Effect on the Pharmacokinetics of Cyclosporine A in Healthy Chinese Volunteers

Frontiers in Pharmacology

Xia Li¹  Uwe Fuhr¹  Max Taubert¹  Xin Tian³  Jingyao Wei³  Ruijuan Liu³  Xiaojian Zhang³  Shuaibing Liu³  Yuanyuan Chang³  Jiali Zhang³  Ji Zhang³ 

[1] Department I of Pharmacology, Faculty of Medicine and University Hospital Cologne, Center for Pharmacology, University of Cologne, Cologne, Germany;Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou, China;

关键词: cyclosporine A;    baicalin;    pharmacokinetics;    non-compartmental analysis;    population pharmacokinetics;    healthy volunteers;   

DOI  :  10.3389/fphar.2019.00518

来源: DOAJ

【 摘 要 】

Despite its narrow therapeutic window and large interindividual variability, cyclosporine A (CsA) is the first-line therapy following organ transplantation. Metabolized mainly by CYP3A and being a substrate of P-glycoprotein (P-gp), CsA is susceptible to drug–drug interactions. Baicalin (BG) is a drug used for adjuvant therapy of hepatitis in traditional Chinese medicine. Since its aglycone baicalein (B) inhibits CYP3A and P-gP, co-administration might affect CsA pharmacokinetics. This study investigated the effect of BG on CsA pharmacokinetics. In a two-period study, 16 healthy volunteers received a single 200 mg oral CsA dose alone (reference period) or in combination with 500 mg BG (test period). Pharmacokinetic evaluation of CsA was carried out using non-compartmental analysis (NCA) and population pharmacokinetics (popPK). Treatments were compared using the standard bioequivalence method. Based on NCA, 90% CIs of AUC and Cmax test-to-reference ratios were within bioequivalence boundaries. In the popPK analysis, a two-compartment model (clearance/F 62.8 L/h, central and peripheral volume of distribution/F 254 L and 388 L) with transit compartments for absorption appropriately described CsA concentrations. No clinically relevant effect of 500 mg BG co-administration on CsA pharmacokinetics was identified and both treatments were well tolerated.

【 授权许可】

Unknown