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Arzneimittelforschung 2008; 58(5): 242-247
DOI: 10.1055/s-0031-1296500
Immunomodulators · Immunostimulants · Immunosuppressants
Editio Cantor Verlag Aulendorf (Germany)

Bioequivalence Studies of Tacrolimus Capsule under Fasting and Fed Conditions in Healthy Male and Female Subjects

Audrey Lainesse
1   Anapharm Inc., Quebec City, Quebec, Canada
,
Saleh Hussain
1   Anapharm Inc., Quebec City, Quebec, Canada
,
Tausif Monif
2   Ranbaxy Laboratories Limited, Haryana, India
,
Simrit Reyar
2   Ranbaxy Laboratories Limited, Haryana, India
,
Sudhakar Koundinya Tippabhotla
2   Ranbaxy Laboratories Limited, Haryana, India
,
Ashish Madan
2   Ranbaxy Laboratories Limited, Haryana, India
,
Nageshwar Rao Thudi
3   Ranbaxy Pharmaceuticals Canada Inc., Toronto, Ontario, Canada
› Author Affiliations
Further Information

Publication History

Publication Date:
15 December 2011 (online)

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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 (LC-MS/MS) method. A non-compartmental method was used for calculation of pharmacokinetic parameters. Under fasting conditions, mean AUC0–t, AUC0–inf and Cmax were comparable between the test (296 ng · h/mL, 318 ng · h/mL and 32 ng/mL, respectively) and the reference formulations (289 ng · h/mL, 309 ng · h/mL and 33 ng/mL, respectively). Tmax was reached between 1.5 and 2 h post-dose. Mean AUC0–t, AUC0–inf and Cmax were also comparable under fed conditions (154 ng · h/mL, 169 ng · h/mL and 7.6 ng/mL, respectively, for the test and 161 ng · h/mL, 176 ng · h/mL and 7.5 ng/mL, respectively, for the reference formulation). Under fed conditions, Tmax 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.

Key words

CAS 104987–11–3 - Immunosuppressants - Tacrolimus, bioequivalence, fasting and fed condition, male and females volunteers, pharmacokinetics
 

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