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.

A randomized, crossover pharmacokinetic study comparing generic tacrolimus vs. the reference formulation in subpopulations of kidney transplant patients

“…Pharmacokinetics of tacrolimus vary widely both between and within patients . Several factors can influence pharmacokinetics of tacrolimus, including intake of fatty food , diarrhea , time interval since transplant , liver dysfunction , variant of gastrointestinal cytochrome P450 (CYP) 3A5*3 isoenzyme expression, and P‐glycoprotein . Moreover, blood concentration of tacrolimus tends to be reduced in certain demographic groups, such as non‐white vs. white recipients , patients with diabetes , and possibly also in females .…”

Effects of Genetic Polymorphisms of CYP2B6 on the Pharmacokinetics of Bupropion and Hydroxybupropion in Healthy Chinese Subjects

“…The clinical protocol was designed in a 2-process, 2-phase, 2-sequence, randomized, and crossover manner over a 2-week washout period between phases [ 18 , 19 ]. After overnight fasting and on day 1, from 6: 00 am to 8: 00 am, the participants could not have any food or water, then 150 mg of BUP (a tablet of 150 mg of BUP SR; Disha, Shandong, or Jingxin, Zhejiang) was orally administrated with 200 mL of water at 8: 00 am.…”

Effects of high-fat diet and CYP2B6 mutants on the pharmacokinetics of bupropion and hydroxybupropion among healthy chinese subjects

“…Drugs, alcohol and caffeine-containing beverages, cigarettes, and nutritional supplements were refrained a week before commencement and throughout the study [15]. [14] The clinical protocols of fasting and feeding study were designed in a randomized two-process, two-phase, twosequence, and crossover manner with a 2-week washout period [16,17]. In fasting study without breakfasting on day 1, subjects orally received 150 mg BUP (a tablet of 150 mg BUP SR; Disha, Shandong, China) or 150 mg BUP (a tablet of 150 mg BUP SR; Jingxin, Zhejiang, China) with 200 mL of water at 8:00 am.…”