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In the control group (<jats:italic>n<\/jats:italic>\u2009=\u20096), rats received a single oral dose of 1\u00a0mg tacrolimus on day 6. In the experimental group (<jats:italic>n<\/jats:italic>\u2009=\u20096), rats received 0.25\u2009g of clarithromycin daily for five consecutive days and then a single oral dose of 1\u00a0mg tacrolimus on day 6. Orbital venous blood (250\u2009\u03bcL) was collected at 0, 0.25, 0.50, 0.75, 1, 2, 4, 8, 12, and 24\u2009h before and after tacrolimus administration. Blood drug concentrations were detected via mass spectrometry. Small intestine and liver tissue samples were collected after rats were euthanized via dislocation, and CYP3A4 and P\u2010glycoprotein (P\u2010gp) protein expression was determined using western blotting. Clarithromycin increased the blood tacrolimus concentration and affected its pharmacokinetic properties in rats. Compared with those in the control group, the AUC<jats:sub>0\u201324<\/jats:sub>, AUC<jats:sub>0\u2013\u221e<\/jats:sub>, AUMC<jats:sub>(0\u2013<jats:italic>t<\/jats:italic>)<\/jats:sub>, and AUMC<jats:sub>(0\u2013\u221e)<\/jats:sub> of tacrolimus in the experimental group were significantly increased, whereas the CLz\/F was significantly lower (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). Simultaneously, clarithromycin significantly inhibited CYP3A4 and P\u2010gp expression in the liver and intestine. Protein expression of CYP3A4 and P\u2010gp in the liver and the intestinal tract was significantly downregulated in the intervention group compared with that in the control group. Clarithromycin significantly inhibited the protein expression of CYP3A4 and P\u2010gp in the liver and intestine, thereby increasing the mean blood concentration and significantly increasing the AUC of tacrolimus.<\/jats:p>","DOI":"10.1111\/fcp.12882","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T06:29:15Z","timestamp":1677047355000},"page":"843-848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of clarithromycin on the pharmacokinetics of tacrolimus and expression of CYP3A4 and P\u2010glycoprotein in rats"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3979-340X","authenticated-orcid":false,"given":"Jinhua","family":"Wen","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"ChenYang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menghua","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7468-5768","authenticated-orcid":false,"given":"Weiqiang","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Wei","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Pharmacy Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/petr.13248"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/PGPM.S107710"},{"key":"e_1_2_9_4_1","first-page":"201","article-title":"Serum concentrations of tacrolimus and CYP3A5*3 in renal transplant patients","volume":"21","author":"Zhu L","year":"2012","journal-title":"Chinese J Pharmacol Toxicol"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2013.08.003"},{"key":"e_1_2_9_6_1","first-page":"117","article-title":"Research progress in drug interaction of tacrolimus","volume":"4","author":"Wang ZH","year":"2011","journal-title":"Clinical Rational Drug Use"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.12793\/tcp.2018.26.2.60"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0250597"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010012\u20101339\u2010x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.14\u20100101"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40842\u2010016\u20100019\u20107"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691\u2010200502000\u201000020"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1C117"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9711179"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2005.12.006"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.17219\/acem\/35254"}],"container-title":["Fundamental &amp; 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