title: Bioequivalence studies of tacrolimus capsule under fasting and fed conditions in healthy male and female subjects.
abstract: The bioequivalence of tacrolimus (CAS 104987-11-3) 5 mg capsules was assessed in two single-dose, open-label, randomIzed 2-way crossover trials with a minimum washout period of 14 days; one trial was conducted under fasting condition (n = 44) and the other one under fed condition (n = 48). Blood samples were collected over a 120-h period and concentrations were assayed using a liquid chromatography tandem mass spectrometry (LCMS/MS) method. A non-compartmental method was used for calculation of pharmacokinetic parameters. Under fasting conditions, mean AUC(0-t), AUC(0-inf) and C(max) were comparable between the test (296 ng x h/mL, 318 ng x h/mL and 32 ng/ mL, respectively) and the reference formulations (289 ng x h/mL, 309 ng x h/mL and 33 ng/mL, respectively). T(max) was reached between 1.5 and 2 h post-dose. Mean AUC(0-t), AUC(0-inf) and C(max) were also comparable under fed conditions (154 ng x h/mL, 169 ng x h/mL and 7.6 ng/mL, respectively, for the test and 161 ng x h/mL, 176 ng x h/mL and 7.5 ng/mL, respectively, for the reference formulation). Under fed conditions, T(max) was reached between 5 and 6 h post-dose. 90% geometric confidence intervals were all within the acceptable 80-125% limit, suggesting bioequivalence between the generic product and the innovator product.
authors.affiliation: Anapharm Inc., Quebec City, Quebec, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Lainesse
authors.forename: Saleh
authors.initials: S
authors.lastname: Hussain
authors.forename: Tausif
authors.initials: T
authors.lastname: Monif
authors.forename: Simrit
authors.initials: S
authors.lastname: Reyar
authors.forename: Sudhakar Koundinya
authors.initials: SK
authors.lastname: Tippabhotla
authors.forename: Ashish
authors.initials: A
authors.lastname: Madan
authors.forename: Nageshwar Rao
authors.initials: NR
authors.lastname: Thudi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D005215:Fasting / Q000502:physiology; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency
chemical_list: D002214:Capsules; D007166:Immunosuppressive Agents; D016559:Tacrolimus