{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:27:42Z","timestamp":1780957662556,"version":"3.54.1"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":4298,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2001,6]]},"abstract":"<jats:p>Tacrolimus (FK506, Prograf\u00ae), marketed for the prophylaxis of organ rejection following allogenic liver or kidney transplantation, is virtually completely metabolized. The major metabolic pathways are P450 3A4\u2010mediated hydroxylation and demethylation. Since P450 hepatic drug\u2010metabolizing enzymes may be impaired din hepatic dysfunction, a study was conducted to characterize oral and intravenous tacrolimus pharmacokinetics in 6 patients with mild hepatic dysfunction and compared with parameters to those from normal subjects obtained in a separate study. Patients received two treatments: a single 0.020 mg\/kg ideal body weight (IBW) IV dose infused over 4 hours and \u223c0.12 mg\/kg IBW orally; normal subjects were dosed at 0.02 mg\/kg 4\u2010hour IV and 5 mg(0.065 mg\/kg) PO. Mean blood pharmacokinetic parameters with mild hepatic dysfunction were as follows: clearance = 0.035 L\/h\/kg, terminal exponential volume of distribution = 2.59 L\/kg, terminal exponential half\u2010life = 60.6 hours (IV), PO maximum blood concentration = 48.2 ng\/mL, time of PO maximum blood concentration = 1.5 hours, and absolute bioavailability = 22.3%. The respective parameters in normal subjects were as follows: 0.040 L\/h\/kg, 1.91 L\/kg, 34.2 hours (IV), 29.7 ng\/mL, 1.6 hours, and 17.8%. Inasmuch as clearance and bioavailability were not substantially different from that in normal subjects, patients with mild hepatic impairment may initially be treated with conventional tacrolimus doses, with subsequent dosage adjustments based on response, toxicity, and therapeutic drug monitoring.<\/jats:p>","DOI":"10.1177\/00912700122010519","type":"journal-article","created":{"date-parts":[[2003,7,19]],"date-time":"2003-07-19T09:38:13Z","timestamp":1058607493000},"page":"628-635","source":"Crossref","is-referenced-by-count":45,"title":["Comparative Tacrolimus Pharmacokinetics: Normal versus Mildly Hepatically Impaired Subjects"],"prefix":"10.1002","volume":"41","author":[{"given":"Ihor","family":"Bekersky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawna","family":"Dressler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ala","family":"Alak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary W.","family":"Boswell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qais A.","family":"Mekki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199529060-00003"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/52.14.1521"},{"key":"e_1_2_1_4_2","first-page":"966","volume-title":"Physicians' Desk Reference","author":"Fujisawa USA","year":"1998"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(97)90150-8"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/00912709922007499"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199512000-00011"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199512000-00010"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199121010-00004"},{"key":"e_1_2_1_10_2","first-page":"57","article-title":"Effect of hepatic dysfunction and T tube clamping on FK 506 pharmacokinetics and trough concentrations","volume":"22","author":"Jain AB","year":"1990","journal-title":"Transplant Proc"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1993.tb04712.x"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.1994.tb01242.x"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.1800600817"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365528909093045"},{"key":"e_1_2_1_15_2","first-page":"1","article-title":"1983 Metropolitan height and weight tables for men and women.","volume":"64","author":"MetLife\u00ae","year":"1983","journal-title":"Stat Bull"},{"key":"e_1_2_1_16_2","volume-title":"Clinical Pharmacokinetics of Tacrolimus","author":"Undre N","year":"1995"},{"key":"e_1_2_1_17_2","first-page":"1098","volume-title":"Physicians' Desk Reference","author":"Fujisawa Healthcare, Inc.","year":"2000"},{"key":"e_1_2_1_18_2","first-page":"2725","article-title":"FK 506 assay past and present\u2010characteristics of FK 506 ELISA","volume":"23","author":"Kobayashi M","year":"1991","journal-title":"Transplant Proc"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1201\/b14095"},{"key":"e_1_2_1_20_2","volume-title":"SAS Procedures Guide","author":"SAS Institute, Inc.","year":"1990"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F00912700122010519","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/00912700122010519","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T14:37:44Z","timestamp":1700404664000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/00912700122010519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,6]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2001,6]]}},"alternative-id":["10.1177\/00912700122010519"],"URL":"https:\/\/doi.org\/10.1177\/00912700122010519","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,6]]}}}