Pharmacokinetics and comparative bioavailability of two oral formulations of tamoxifen citrate in healthy male volunteers

Aim To access the pharmacokinetics and comparative bioavailability of two tamoxifen citrate (TAM) formulations in 20 healthy Chinese male subjects under fasting conditions. Methods TAM test capsules and reference tablets were administered as a single dose on two treatment days separated by a 3-week washout period. After dosing, serial blood samples were collected for a period of 72 hr, and plasma TAM concentrations were determined by a sensitive, selective, reproducible and accurate liquid chromatography-tandem mass spectometry (LC/MS/MS) method. Pharmacokinetic parameters were analyzed by the non-compartmental method. Results The main pharmacokinetic parameters of tamoxifen citrate test and reference formulations were as follow: Tmax were (3.90 ±0.91) and (3.95 ±1.10) h, Cmax were (108.06±19.84) and (101.26 ±16.48) μg·L, T1/2 were (53.52 ±14.41) and (51.67 ±8.94) h, AUC0-72 were (3073.71 ±439.08) and (3148.75±373.70) μg·h·L, AUC0-∞ were (5074.85±1082.24) and (5121.18 ±902.00) μg·h·L, respectively. The relative bioavailability of test formulations was (97.88 ±10.79) %. No significant differences between the two formulations were found, and the parametric confidence intervals (90%) of the mean values of the pharmacokinetic characteristics for test/reference ratio were in each case well within the bioequivalence acceptable ranges of 0.8-1.25 and 0.70-1.43 respectively for AUC and Cmax. Conclusion The results indicate that the two TAM formulations are equivalent in the rate and extent of absorption.