Effect of Tacrolimus on the pharmacokinetics of bioactive lignans of Wuzhi tablet (Schisandra sphenanthera extract) and the potential roles of CYP3A and P-gp |
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| Institution: | 1. Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China;2. Guangdong Food and Drug Vocational College, Guangzhou, China;3. The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;4. Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China;1. Department of Clinical Pharmacology, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia;2. Discipline of Pharmacology, School of Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia;3. Central Northern Adelaide Renal Transplantation Services, The Royal Adelaide Hospital, Adelaide, SA 5000, Australia;4. Department of Internal Medicine, Renal Transplant Unit, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands;1. College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea;2. Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-myeon, 893-5, Hwaseong, Gyeonggi-Do 445-913, South Korea;3. College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea;1. Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China;2. Laboratory of Natural Medicine, School of Forestry and Bio-technology, Zhejiang A&F University, Lin’an 311300, China;3. Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;4. The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310000, China;1. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China;2. Department of Cardiology, Yanzhou Affiliated Hospital of Jining Medical College, Yanzhou, Shandong, China;1. School of Pharmaceutical Science, Shandong University, Jinan 250012, China;2. Department of Pharmacy, Shandong Provincial Qian Foshan Hospital, Jinan 250014, China;3. Institute of Biopharmaceuticals of Shandong Province, Jinan 250101, China;1. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong Province 510006, PR China;2. School of Pharmaceutical Sciences, Hainan Medical University, Haikou, Hainan Province 571199, PR China |
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| Abstract: | We recently reported that Wuzhi tablet (WZ), a preparation of the ethanol extract of Wuweizi (Schisandra sphenanthera), had significant effects on blood concentrations of Tacrolimus (FK506) in renal transplant recipients and rats. The active lignans in WZ are schisandrin A, schisandrin B, schisandrin C, schisandrol A, schisandrol B, schisantherin A, and schisantherin B. Until now, whether the pharmacokinetics of these lignans in WZ would be affected by FK506 remained unknown. Therefore, this study aimed to investigate whether and how FK506 affected pharmacokinetics of lignans in WZ in rats and the potential roles of CYP3A and P-gp. After a single oral co-administration of FK506 and WZ, the blood concentration of lignans in WZ was decreased by FK506; furthermore, the AUC of schisantherin A, schisandrin A, schisandrol A and schisandrol B was only 64.5%, 47.2%, 55.1% and 57.4% of that of WZ alone group, respectively. Transport study in Caco-2 cells showed that these lignans were not substrates of P-gp, suggesting decreased blood concentration of lignans by FK506 was not via P-gp pathway. Metabolism study in the human recombinant CYP 3A showed that these lignans had higher affinity to CYP3A than that of FK506, and thus had a stronger CYP3A-mediated metabolism. It was concluded that the blood concentrations of these lignans were decreased and their CYP3A-mediated metabolisms were increased in the presence of FK506 since these lignans had higher affinity to CYP3A. |
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| Keywords: | Tacrolimus Wuzhi tablet Lignans Pharmacokinetics Herb–drug interaction |
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