Pharmacokinetics and Bioequivalence Research of Tacrolimus Sustained Release Capsule in Beagle Dogs

OBJECTIVE To investigate pharmacokinetic and bioequivalence of tacrolimus sustained release capsule in beagle dogs. METHODS Six beagle dogs were randomly divided into 2 groups. A single oral dose of 3 mg of test or reference capsules were delivered to each dog in an open crossover test. The blood concentration of tacrolimus was determined by LC-MS/MS detection, and the pharmacokinetic parameters were calculated with WinNonlin 6.3 program by a computer. Based on the parameters of pharmacokinetic and relative bioavailability, the bioequivalence of tacrolimus was evaluated. RESULTS The pharmacokinetic parametes of the test and reference preperations were as follows: T_max was (1.08±0.41)h and (0.83±0.13)h, C_max was (11.63±1.35)ng·mL^-1 and (14.83±4.70)ng·mL^-1, AUC_0-48 was (62.93±32.06)h·ng·mL^-1 and (62.89±28.14)h·ng·mL^-1, t_1/2 was (10.90±4.26)h and (10.99±3.12)h in 2 groups respectively. After taking oral test capsule, beagle dog shows no noticeable T_max，t_1/2 variation between test and reference capsule; The C_max is about 85.34% of the reference capsule that is located within the 90% confidence interval of 87.21%-102.16%; The relative bioequivalence (AUC_last，test/AUC_{last，reference}) is 99.42%, that is with in the 90% confidence interval of 85.53%-115.56%, it shows that the test and reference capsule is close in effects. CONCLUSION The test and reference preparation of tacrolimus are bioequivalent.