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3.3.1. Schisandra sphenanthera

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3.3.1. Schisandra sphenanthera A Schisandra sphenanthera ethanol extract (SchE) is a herbal medicine also referred to as a Wuzhi capsule, or a Wuhzi tablet, which has been used in the traditional Chinese medicine for thousands of years in cases of hepatitis, hepatic and renal insufficiency, menstrual dysfunction, neurosis and others [74,75,76,77]. It is often prescribed in Chinese transplant patients for tacrolimus-induced hepatitis treatment as a liver-protective agent [77,78]. Studies have shown that the co-administration of Wuhzi tablets and tacrolimus may significantly increase tacrolimus blood concentration. Schisantherin A (STA) and schisandrin A (SIA), the main active agents of SchE, inhibit CYP3A4/5 by both reversible inhibition and the permanent loss of enzyme activity through its destruction [76,79]. Other SchE components, schisandrin B and gomisin A, were found to inhibit P-glycoprotein, whereas gomisin C competitively inhibited and irreversibly deactivated CYP3A [78]. Tacrolimus is metabolized by CYP3A isoenzymes and undergoes P-glycoprotein-mediated transport; therefore, an interaction should be expected [4,76,80]. Tacrolimus blood concentrations increased 1.57–4.66-fold following SchE administration [76]. Moreover, parameters, such as the AUC, AUMC and Cmax of tacrolimus, were reported to increase significantly, although in terms of CL/F and V/F a significant decrease was observed [78,81]. The SchE effect on Cmax and AUC in rats was dose-dependent and the maximum mean plasma concentration of tacrolimus was achieved at 450 mg/kg [77]. Interestingly, a higher SchE dose did not result in an increase in tacrolimus concentration. Furthermore, a single SchE dose administration resulted in a higher mean plasma concentration and AUC compared to a multiple SchE dosing [77]. Despite the remarkable increase in the blood AUC of tacrolimus, no significant changes were found in rat tissue concentrations [82]. Moreover, studies on CYP3A5 polymorphism showed that SchE effect was more pronounced in the CYP3A5 expressers compared to the non-expressers [79,81,83]. An increase in tacrolimus concentration was lower, although still significant when combined with a long-term prednisone treatment [84]. Xin et al. reported lower mean creatinine levels and higher mean BUN levels in healthy volunteers after SchE and tacrolimus co-administration [78]. In terms of liver function, ALT and AST levels significantly decreased following 6-month SchE treatment in renal transplant patients receiving tacrolimus [85]. SchE administration in renal transplant recipients not only did not deteriorate graft function but was found to have a protective effect on its survival [81]. Side effects, such as hyperkalaemia or fever, were reported after SchE and tacrolimus co-administration and were accounted for as a result of an increased tacrolimus blood concentration [78,86]. Several population pharmacokinetic models have been developed to support the individualization of tacrolimus dosing for different groups: renal transplant recipients [81,83,85,87,88], liver transplant recipients [89,90], cardiac transplant recipients [91,92], patients with refractory nephrotic syndrome [93,94], membranous nephropathy [95,96], lupus nephritis [97,98] or myasthenia gravis [99]. SchE may significantly increase tacrolimus bioavailability and reduce its therapeutic costs by 40–60%, nevertheless, authors highly recommend blood tacrolimus concentration monitoring while co-administering with SchE [78,79,82,85].

Befund HOS-368838 · tacrolimus · HOS-085202 · Originalquelle ↗

Controversial Interactions of Tacrolimus with Dietary Supplements, Herbs and Food ↗

© 2022 by the authors. Miłosz Miedziaszczyk; Aleksander Bajon; Ewelina Jakielska; Marta Primke; Jędrzej Sikora; Dagmara Skowrońska; Ilona Idasiak-Piechocka. Controversial Interactions of Tacrolimus with Dietary Supplements, Herbs and Food. DOI: 10.3390/pharmaceutics14102154 · CC BY 4.0

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• 74.Chen Z., Liu F., Zheng N., Guo M., Bao L., Zhan Y., Zhang M., Zhao Y., Guo W., Ding G. Wuzhi capsule (Schisandra sphenanthera extract) attenuates liver steatosis and inflammation during non-alcoholic fatty liver disease development. Biomed. Pharmacother. 2019;110:285–293. doi: 10.1016/j.biopha.2018.11.069.
• 75.Lu Y., Chen D.F. Analysis of Schisandra chinensis and Schisandra sphenanthera. J. Chromatogr. A. 2009;1216:1980–1990. doi: 10.1016/j.chroma.2008.09.070.
• 76.Zhang H., Bu F., Li L., Jiao Z., Ma G., Cai W., Zhuang X., Lin H.S., Shin J.G., Xiang X. Prediction of Drug-Drug Interaction between Tacrolimus and Principal Ingredients of Wuzhi Capsule in Chinese Healthy Volunteers Using Physiologically-Based Pharmacokinetic Modelling. Basic Clin. Pharmacol. Toxicol. 2018;122:331–340. doi: 10.1111/bcpt.12914.
• 77.Wei H., Tao X., Di P., Yang Y., Li J., Qian X., Feng J., Chen W. Effects of traditional Chinese medicine Wuzhi capsule on pharmacokinetics of tacrolimus in rats. Drug Metab. Dispos. 2013;41:1398–1403. doi: 10.1124/dmd.112.050302.
• 78.Xin H.W., Wu X.C., Li Q., Yu A.R., Zhu M., Shen Y., Su D., Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers. Br. J. Clin. Pharmacol. 2007;64:469–475. doi: 10.1111/j.1365-2125.2007.02922.x.
• 79.He Q., Bu F., Zhang H., Wang Q., Tang Z., Yuan J., Lin H.S., Xiang X. Investigation of the Impact of CYP3A5 Polymorphism on Drug-Drug Interaction between Tacrolimus and Schisantherin A/Schisandrin A Based on Physiologically-Based Pharmacokinetic Modeling. Pharmaceuticals. 2021;14:198. doi: 10.3390/ph14030198.
• 4.Schmidt L.E., Dalhoff K. Food-drug interactions. Drugs. 2002;62:1481–1502. doi: 10.2165/00003495-200262100-00005.
• 80.Qin X.L., Chen X., Wang Y., Xue X.P., Wang Y., Li J.L., Wang X.D., Zhong G.P., Wang C.X., Yang H., et al. In vivo to in vitro effects of six bioactive lignans of Wuzhi tablet (Schisandra sphenanthera extract) on the CYP3A/P-glycoprotein-mediated absorption and metabolism of tacrolimus. Drug Metab. Dispos. 2014;42:193–199. doi: 10.1124/dmd.113.053892.
• 81.Yan L., Yang Z.Q., Shi Y.Y., Ren J., Yang C.L., Wan Z.L., Bai Y.J., Luo L.M., Wang L.L., Li Y. Effects of Wuzhi Capsules on Blood Concentration of Tacrolimus in Renal Transplant Recipients. Ann. Transplant. 2019;24:594–604. doi: 10.12659/AOT.918980.
• 82.Qin X.L., Bi H.C., Wang C.X., Li J.L., Wang X.D., Liu L.S., Chen X., Huang M. Study of the effect of Wuzhi tablet (Schisandra sphenanthera extract) on tacrolimus tissue distribution in rat by liquid chromatography tandem mass spectrometry method. Biomed Chromatogr. 2010;24:399–405. doi: 10.1002/bmc.1305.
• 83.Li J., Chen S., Qin X., Fu Q., Bi H., Zhang Y., Wang X., Liu L., Wang C., Huang M. Wuzhi tablet (Schisandra sphenanthera Extract) is a Promising Tacrolimus-Sparing Agent for Renal Transplant Recipients Who are CYP3A5 Expressers: A Two-Phase Prospective Study. Drug Metab. Dispos. 2017;45:1114–1119. doi: 10.1124/dmd.117.076737.
• 84.Qin X.L., Yu T., Li L.J., Wang Y., Gu H.M., Wang Y.T., Huang M., Bi H.C. Effect of long-term co-administration of Wuzhi tablet (Schisandra sphenanthera extract) and prednisone on the pharmacokinetics of tacrolimus. Phytomedicine. 2013;20:375–379. doi: 10.1016/j.phymed.2012.11.008.
• 85.Xin H.W., Li Q., Wu X.C., He Y., Yu A.R., Xiong L., Xiong Y. Effects of Schisandra sphenanthera extract on the blood concentration of tacrolimus in renal transplant recipients. Eur. J. Clin. Pharmacol. 2011;67:1309–1311. doi: 10.1007/s00228-011-1075-7.
• 86.Chen T., Lin M., Lu J. Hyperkalemia induced by tacrolimus combined with Wuzhi-capsule following renal transplantation: One case report. J. Clin. Rehabil. Tissue Eng. Res. 2011;44:8341–8343.
• 87.Chen L., Yang Y., Wang X., Wang C., Lin W., Jiao Z., Wang Z. Wuzhi Capsule Dosage Affects Tacrolimus Elimination in Adult Kidney Transplant Recipients, as Determined by a Population Pharmacokinetics Analysis. Pharmgenom. Pers. Med. 2021;14:1093–1106. doi: 10.2147/PGPM.S321997.
• 88.Wang D.D., Chen X., Li Z.P. Wuzhi capsule and haemoglobin influence tacrolimus elimination in paediatric kidney transplantation patients in a population pharmacokinetics analysis: A retrospective study. J. Clin. Pharm. Ther. 2019;44:611–617. doi: 10.1111/jcpt.12828.
• 89.Wang D.D., Chen X., Fu M., Zheng Q.S., Xu H., Li Z.P. Model extrapolation to a real-world dataset: Evaluation of tacrolimus population pharmacokinetics and drug interaction in pediatric liver transplantation patients. Xenobiotica. 2020;50:371–379. doi: 10.1080/00498254.2019.1631505.
• 90.Chen X., Wang D.D., Xu H., Li Z.P. Population pharmacokinetics and pharmacogenomics of tacrolimus in Chinese children receiving a liver transplant: Initial dose recommendation. Transl. Pediatr. 2020;9:576–586. doi: 10.21037/tp-20-84.
• 91.Gong Y., Yang M., Sun Y., Li J., Lu Y., Li X. Population pharmacokinetic analysis of tacrolimus in Chinese cardiac transplant recipients. Eur. J. Hosp. Pharm. 2020;27:e12–e18. doi: 10.1136/ejhpharm-2018-001764.
• 92.Han Y., Zhou H., Cai J., Huang J., Zhang J., Shi S.J., Liu Y.N., Zhang Y. Prediction of tacrolimus dosage in the early period after heart transplantation: A population pharmacokinetic approach. Pharmacogenomics. 2019;20:21–35. doi: 10.2217/pgs-2018-0116.
• 93.Chen X., Wang D.D., Xu H., Li Z.P. Optimization of initial dosing scheme of tacrolimus in pediatric refractory nephrotic syndrome patients based on CYP3A5 genotype and coadministration with wuzhi-capsule. Xenobiotica. 2020;50:606–613. doi: 10.1080/00498254.2019.1669844.
• 94.Lu T., Zhu X., Xu S., Zhao M., Huang X., Wang Z., Zhao L. Dosage Optimization Based on Population Pharmacokinetic Analysis of Tacrolimus in Chinese Patients with Nephrotic Syndrome. Pharm. Res. 2019;36:45. doi: 10.1007/s11095-019-2579-6.
• 95.Sun Z., Ren M., Wu Q., Du X. Co-administration of Wuzhi capsules and tacrolimus in patients with idiopathic membranous nephropathy: Clinical efficacy and pharmacoeconomics. Int. Urol. Nephrol. 2014;46:1977–1982. doi: 10.1007/s11255-014-0801-3.
• 96.Zhang Z., Lu X., Dong L., Ma J., Fan X. Clinical observation on the effect of Wuzhi soft capsule on FK506 concentration in membranous nephropathy patients. Medicine. 2019;98:e18150. doi: 10.1097/MD.0000000000018150.
• 97.Chen X., Wang D., Xu H., Li Z. Initial dose optimization of tacrolimus for children with systemic lupus erythematosus based on the CYP3A5 polymorphism and coadministration with Wuzhi capsule. J. Clin. Pharm. Ther. 2020;45:309–317. doi: 10.1111/jcpt.13072.
• 98.Chen X., Wang D.D., Xu H., Li Z.P. Population pharmacokinetics model and initial dose optimization of tacrolimus in children and adolescents with lupus nephritis based on real-world data. Exp. Ther. Med. 2020;20:1423–1430. doi: 10.3892/etm.2020.8821.
• 99.Liu J., Guo Y.P., Jiao Z., Zhao C.B., Wu H., Li Z.R., Cai X.J., Xi J.Y. Population Pharmacokinetic Analysis of Tacrolimus in Adult Chinese Patients with Myasthenia Gravis: A Prospective Study. Eur. J. Drug Metab. Pharmacokinet. 2020;45:453–466. doi: 10.1007/s13318-020-00609-5.