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Effect of Low‐ and High‐Fat Meals on Tacrolimus Absorption following 5 mg Single Oral Doses to Healthy Human Subjects
Author(s) -
Bekersky Ihor,
Dressler Dawna,
Mekki Qais A.
Publication year - 2001
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 - 10.1177/00912700122009999
Subject(s) - tacrolimus , cmax , bioavailability , medicine , pharmacokinetics , crossover study , meal , absorption (acoustics) , area under the curve , oral administration , pharmacology , gastroenterology , zoology , urology , transplantation , placebo , biology , alternative medicine , physics , pathology , acoustics
Tacrolimus (FK506, Prograf®) is a macrolide lactone antibiotic widely used by the oral route for the prophylaxis of organ rejection in patients who have received allogenic liver or kidney transplants. This study investigated the influence of a high‐ versus a low‐fat meal, relative to the fasting state (three treatments total), on the rate and extent of tacrolimus absorption following a single 5 mg oral dose. The protocol employed a three‐period, randomized, crossover design employing 5 × 1 mg capsules in 15 healthy male nonsmoking, drug‐free volunteers, 20 to 45 years of age, who were within 15% of their ideal body weight. Food had a clinically significant effect in reducing relative bioavailability, as well as slowing absorption, but did not affect terminal exponential half‐life (∼34 hours). Mean maximum tacrolimus blood concentration (C max ) values were 25.6, 5.88, and 9.03 ng/mL for the fasting, high‐fat, and low‐fat treatments, respectively; mean area under the blood concentration‐time curve (AUC (0‐∞) ) values were 272, 181, and 201 (ng/mL)‐h, respectively; and mean time of C max (t max ) values were 1.37, 6.47, and 3.20 hours, respectively. Differences in parameters between the fasting and each fed treatment were statistically significantly different (p < 0.05). Statistically significant differences also existed in t max between the two meals. Results also indicated the safety of single 5 mg oral tacrolimus doses administered to healthy volunteers.