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For this reason, inhibitors, or inducers of intestinal P\u2010gp may alter the plasma concentration of sofosbuvir and increase or decrease its efficacy causing a significant change in its pharmacokinetic parameters. The purpose of the study was to evaluate the pharmacokinetic interaction between either aged garlic or ginkgo biloba extracts with sofosbuvir through targeting P\u2010gp as well as possible toxicities in rats. Rats were divided into four groups and treated for 14\u00a0days with saline, verapamil (15\u00a0mg\/kg, PO), aged garlic extract (120\u00a0mg\/kg, PO), or ginkgo biloba extract (25\u00a0mg\/kg, PO) followed by a single oral dose of sofosbuvir (40\u00a0mg\/kg). Validated LC\u2010MS\/MS was used to determine sofosbuvir and its metabolite GS\u2010331007 in rat plasma. Aged garlic extract caused a significant decrease of sofosbuvir AUC<jats:sub>(0\u2212t)<\/jats:sub> by 36%, while ginkgo biloba extract caused a significant increase of sofosbuvir AUC<jats:sub>(0\u2212t)<\/jats:sub> by 11%. Ginkgo biloba extract exhibited a significant increase of the sofosbuvir t<jats:sub>1\/2<\/jats:sub> by 60%, while aged garlic extract significantly increased the clearance of sofosbuvir by 63%. The pharmacokinetic parameters of GS\u2010331007 were not affected. The inhibitory action of ginkgo biloba on P\u2010gp and the subsequent increase in the sofosbuvir plasma concentration did not show a significant risk of renal or hepatic toxicity. Conversely, although aged garlic extracts increased intestinal P\u2010gp expression, they did not alter the C<jats:sub>max<\/jats:sub> and T<jats:sub>max<\/jats:sub> of sofosbuvir and did not induce significant hepatic or renal toxicities.<\/jats:p>","DOI":"10.1002\/bdd.2326","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T10:34:44Z","timestamp":1660732484000},"page":"152-162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of aged garlic and ginkgo biloba extracts on the pharmacokinetics of sofosbuvir in rats"],"prefix":"10.1002","volume":"43","author":[{"given":"Abanoub K.","family":"Wasef","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Department Faculty of Pharmacy Sinai University (Kantara Campus)  Ismailia Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara A.","family":"Wahdan","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department Faculty of Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noha M.","family":"Saeed","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department Faculty of Pharmacy Egyptian Russian University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2951-4892","authenticated-orcid":false,"given":"Ebtehal","family":"El\u2010Demerdash","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department Faculty of Pharmacy Ain Shams University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2017.06.005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2011.11.011"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00244\u2010010\u20109494\u20105"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2008.12.005"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920013804545188"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK\u201010\u2010RG\u2010053"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.32.694"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200211209050640"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2004.10.002"},{"key":"e_1_2_9_11_1","volume-title":"Handbook of histopathological and histochemical techniques: Including museum techniques","author":"Culling C. 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