title: Effect of Wuzhi tablet (Schisandra sphenanthera extract) on the pharmacokinetics of cyclosporin A in rats.
abstract: In our previous reports, Wuzhi tablet (an herbal preparation of ethanol extract of Wuweizi (Schisandra sphenanthera)) can significantly increase the blood concentration of tacrolimus and paclitaxel in rats by inhibiting the CYP3A-mediated metabolism and the P-gp-mediated efflux. Cyclosporin A (CsA), a well-known immunosuppressant agent, is also a substrate of CYP3A and P-gp. Therefore, this study aimed to investigate whether and how WZ affects pharmacokinetics of CsA in rats. The AUC0-48 h and Cmax of CsA were increased by 40.1% and 13.1%, respectively, with a single oral co-administration of WZ and high dose of CsA (37.8 mg/kg). Interestingly, after a single oral co-administration of WZ and low dose of CsA (1.89 mg/kg), the AUC0-36 h and Cmax of CsA were dramatically increased by 293.1% (from 1103.2 ± 293.0 to 4336.5 ± 1728.3 ng.h/mL; p < 0.05) and 84.1% (from 208.5 ± 67.9 to 383.1 ± 92.5 ng/mL; p < 0.05), respectively. The CL/F was decreased from 1.7 L/h/kg to 0.5 L/h/kg. Thus, the effect of WZ on high dose of CsA was not significant, but pharmacokinetic parameters of CsA at low dose were significantly influenced by co-administration of WZ. The herb-drug interaction should be taken into consideration at this situation.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xin-ping
authors.initials: XP
authors.lastname: Xue
authors.forename: Xiao-ling
authors.initials: XL
authors.lastname: Qin
authors.forename: Chenshu
authors.initials: C
authors.lastname: Xu
authors.forename: Guo-ping
authors.initials: GP
authors.lastname: Zhong
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Hui-chang
authors.initials: HC
authors.lastname: Bi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D032141:Schisandra / Q000737:chemistry; D013607:Tablets
chemical_list: D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D013607:Tablets; C582515:wuzhi; D016572:Cyclosporine