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Effects of Rifampin on Tacrolimus Pharmacokinetics in Healthy Volunteers
Author(s) -
Hebert Mary F.,
Fisher Richard M.,
Marsh Christopher L.,
Dressler Dawna,
Bekersky Ihor
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912709922007499
Subject(s) - tacrolimus , pharmacokinetics , pharmacology , cyp3a4 , medicine , bioavailability , drug interaction , cyp3a , oral administration , dosing , concomitant , transplantation , metabolism , cytochrome p450
Tacrolimus is a marketed immunosuppressant used in liver and kidney transplantation. It is subject to extensive metabolism by CYP3A4 and is a substrate for P‐glycoprotein‐mediated transport. A pharmacokinetic interaction with rifampin, an antituberculosis agent and potent inducer of CYP3A4 and P‐glycoprotein, and tacrolimus was evaluated in six healthy male volunteers. Tacrolimus was administered at doses of 0.1 mg/kg orally and 0.025 mg/kg/4 hours intravenously. The pharmacokinetics of tacrolimus were obtained from serial blood samples collected over 96 hours, after single oral and intravenous administration prior to and during an 18‐day concomitant rifampin dosing phase. Coadministration of rifampin significantly increased tacrolimus clearance (36.0 ± 8.1 ml/hr/kg vs. 52.8 ± 9.6 ml/hr/kg; p = 0.03) and decreased tacrolimus bioavailability (14.4% ± 5.7% vs. 7.0% ± 2.7%; p = 0.03). Rifampin appears to induce both intestinal and hepatic metabolism of tacrolimus, most likely through induction of CYP3A and P‐glycoprotein in the liver and small bowel .