Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers

What is already known about this subject Schisandra sphenanthera extract (SchE) and tacrolimus are often co-administrated in treating renal and liver transplant recipients in China. We discovered occasionally that blood tacrolimus concentrations are markedly increased in some patients who receive tacrolimus and concomitant SchE. This is the first study to investigate the effects of SchE on the pharmacokinetics of tacrolimus. What this study adds Following administration of SchE in healthy volunteers, the mean AUC, AUMC and C-max of tacrolimus substantially increases, whereas its CL/F and V/F decreases significantly. Blood tacrolimus concentrations need to be closely monitored and dose adjustments of tacrolimus have to be made accordingly in the presence of SchE. To assess the effect of Schisandra sphenanthera extract (SchE) on the pharmacokinetics of tacrolimus in healthy volunteers. Twelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 13 days. Pharmacokinetic investigations of oral tacrolimus administration at 2 mg were performed both before and at the end of the SchE treatment period. Whole blood tacrolimus concentrations were determined by enzyme-linked immunosorbent assay. Estimated pharmacokinetic parameters before and with SchE were calculated with noncompartmental techniques. Following administration of SchE, the average percentage increases of individual increases in AUC, AUMC and C-max of tacrolimus were 164.2% [95% confidence interval (CI) 70.1, 258.4], 133.1% (95% CI 49.5, 261.3) and 227.1% (95% CI 155.8, 298.4), respectively (P < 0.01 or 0.05). On average, there was a 36.8% (95% CI 13.4, 60.2) increase in tacrolimus t(max) (P < 0.01). The average percentage decreases in CL/F and V/F were 49.0% (95% CI 31.1, 66.9) and 53.7% (95% CI 40.1, 67.4), respectively (P < 0.01). SchE can increase the oral bioavailability of tacrolimus. The results of this study will add important information to the interaction area between drugs and herbal products.