title: Bioequivalence of 1 and 5 mg tacrolimus capsules using a replicate study design.
abstract: Tacrolimus (FK506, Prograf) is marketed for the prophylaxis of organ rejection following allogenic liver or kidney transplantation. A previously conducted, randomized, 24-subject, crossover bioavailability study of 1 and 5 mg capsules (one period each) failed to demonstrate bioequivalence. A single-dose, four-period, four-sequence, randomized, crossover, replicate study (N = 32) was therefore used to evaluate the bioequivalence of the marketed 1 and 5 mg capsules in healthy volunteers. Tacrolimus blood concentrations were measured serially over 72 hours using a commercially available ELISA assay. Noncompartmental pharmacokinetic parameters were determined. Ninety percent CIs of log-transformed parameter ratios were 90.5-101.9, 87.1-101.7, and 89.7-103.8 for Cmax, AUC0-t, and AUC0-infinity, respectively. Since all values were within 80% to 125%, the capsules are bioequivalent. Based on %CVs, intersubject variability was approximately two to three times greater than intrasubject variability. The safety of single 5 mg oral tacrolimus doses administered to healthy volunteers at 7-day intervals was also ascertained.
authors.affiliation: Fujisawa Healthcare, Inc., Deerfield, IL 60015-2548, USA.
authors.forename: I
authors.initials: I
authors.lastname: Bekersky
authors.forename: D
authors.initials: D
authors.lastname: Dressler
authors.forename: W
authors.initials: W
authors.lastname: Colburn
authors.forename: Q
authors.initials: Q
authors.lastname: Mekki
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D000328:Adult; D019540:Area Under Curve; D018771:Arthralgia / Q000139:chemically induced; D002214:Capsules; D018592:Cross-Over Studies; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D007719:Knee Joint; D008297:Male; D011693:Purpura / Q000139:chemically induced; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
chemical_list: D002214:Capsules; D007166:Immunosuppressive Agents; D016559:Tacrolimus