TY - JOUR T1 - The Disposition of <sup>14</sup>C-Labeled Tacrolimus after Intravenous and Oral Administration in Healthy Human Subjects JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 633 LP - 636 VL - 27 IS - 6 AU - A. Möller AU - K. Iwasaki AU - A. Kawamura AU - Y. Teramura AU - T. Shiraga AU - T. Hata AU - A. Schäfer AU - N. A. Undre Y1 - 1999/06/01 UR - http://dmd.aspetjournals.org/content/27/6/633.abstract N2 - Tacrolimus is a macrolide lactone with potent immunosuppressive properties. It has been shown in clinical studies to prevent allograft rejection. The pharmacokinetics of tacrolimus in healthy subjects and transplant patients has been described in earlier studies using immunoassay methods; however, detailed information on the absorption, distribution, metabolism, and excretion of tacrolimus using a radiolabeled drug is lacking. The objective of the present study was to characterize the disposition of tacrolimus after single i.v. (0.01 mg/kg) and oral (0.05 mg/kg) administration of 14C-labeled drug in six healthy subjects. Tacrolimus was absorbed rapidly after oral dosing with a mean Cmax andTmax of 42 ng/ml and 1 h, respectively. The oral bioavailability was about 20%. After i.v. and oral dosing, most of the administered dose was recovered in feces, suggesting that bile is the principal route of elimination. Urinary excretion accounted for less than 3% of total administered dose. In systemic circulation, unchanged parent compound accounted for nearly all the radioactivity; however, less than 0.5% of unchanged drug was detectable in feces and urine. The excretion of the metabolites was formation-rate-limited. The mean total body clearance at 37.5 ml/min was equivalent to about 3% of the liver blood flow. Renal clearance was less than 1% of the total body clearance. The mean elimination half-life was 44 h. The American Society for Pharmacology and Experimental Therapeutics ER -