{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T17:23:45Z","timestamp":1788715425126,"version":"build-2803163510"},"reference-count":13,"publisher":"Bentham Science Publishers Ltd.","issue":"2","funder":[{"name":"First Affiliated Hospital of Nanchang University, China","award":["20192BCBL23018"],"award-info":[{"award-number":["20192BCBL23018"]}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["CDM"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:sec>\n<jats:title>Objective:<\/jats:title>\n<jats:p>This study aimed to investigate the effects of clarithromycin and ketoconazole on the\npharmacokinetic properties of tacrolimus in different CYP3A4 genotype recombinant metabolic enzyme systems,\nso as to understand the drug interactions and their mechanisms further.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Method:<\/jats:title>\n<jats:p>The experiment was divided into three groups: a blank control group, CYP3A4*1 group and\nCYP3A4*18 recombinant enzyme group. Each group was added with tacrolimus (FK506) of a series of concentrations.\nThen 1 umol\/L clarithromycin or ketoconazole was added to the recombinant enzyme group and\nincubated in the NADPH system for 30 minutes to examine the effects of clarithromycin and ketoconazole on\nthe metabolizing enzymes\u2019 activity of different genotypes. The remaining concentration of FK506 in the reaction\nsystem was determined using UPLC-MS\/MS, and the enzyme kinetic parameters were calculated using\nthe software.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>The metabolism of CYP3A4*18 to FK506 was greater than that of CyP3\u04104*1B. Compared with the\nCYP3A4*1 group, the metabolic rate and clearance of FK506 in the CYP3A4*18 group significantly increased,\nwith Km decreasing. Clarithromycin and ketoconazole inhibit the metabolism of FK506 by affecting\nthe enzyme activity of CYP3A4*1B and CYP3A4*18B. After adding clarithromycin or ketoconazole, the\nmetabolic rate of FK506 significantly decreased in CYP3A4*1 and CYP3A4*18, with Km increasing, Vmax\nand Clint decreasing.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>Compared with CYP3A4*1, CYP3A4*18 has a greater metabolism of FK506, clarithromycin\nand ketoconazole can inhibit both the enzymatic activities of CYP3A4*1 and CYP3A4*18, consequently affecting\nthe metabolism of FK506 and the inhibitory on CYP3A4*1 is stronger.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/0113892002286019240315052145","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T07:22:57Z","timestamp":1711351377000},"page":"174-177","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of Clarithromycin and Ketoconazole on FK506 Metabolism in Different\nCYP3A4 Genotype Recombinant Metabolic Enzyme Systems"],"prefix":"10.2174","volume":"25","author":[{"given":"Jinhua","family":"Wen","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanchang University, Nanchang, 330006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghua","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanchang University, Nanchang, 330006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiang","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanchang University, Nanchang, 330006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1097\/00000658-197802000-00005","volume":"187","author":"Munda R.","year":"1978","unstructured":"Munda R.; Alexander J.W.; First M.R.; Gartside P.S.; Fidler J.P.; Pulmonary infections in renal transplant recipients. 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