The Study Of The Bioequivalence-evaluating Methods Of Anethole Trithione Preparations

In this paper, Anethole Trithione (AT) was selected as model drug to examine whether using a relative standard substance as a substitute of the real standard substance to evaluate the bioequivalence of different drug preparations was rational and feasible when the real standard substance was out of reach. High-performance liquid chromatograph (HPLC)-assays with UV detection (λ=346nm) were presented and validated for the quantitative analysis of AT and ATX (the metabolite of AT) respectively. 20 healthy volunteers were randomized to a self-controlled, crossover study comparing two preparations: AT capsule (T) and AT tablet (R). 18 subjects completed the study and plasma samples were collected.By using AT as a relative standard substance to quantitate all samples and calculate the results, one-compartment models were found preferable in all volunteers. The main pharmacokinetic parameters of the two formulations ( T and R ) were as follows: An AUC₀→t of 2091.26 ±628.86ng.h.ml^-1 for T and of 2043.71±652.29ng.h.ml^-1 for R; A T_max of 2.42 ±0.46 h for T and of 2.58±0.65 h for R; A C_max of 621.00 ±178.82 ng.ml^-1 for T and of 611.67±171.51 ng.ml^-1 for R. After its oral administration to human, the relative bioavailability of T was 103.45 % ±11.75%. Paired analysis indicated that T_max, C_max and AUC₀→t did notdiffer between T and R and both preparations were bioequivalent.ATX, the standard substance, was used to quantitate all the samples again and the results were as follows: one-compartment model; An AUCo-t of 2730.861845.09 ng-h-ml"1 for T and of 2664.39+ SOS^ng-h-mr1 for R; A T? of 2.56 ±0.45 h for T and of 2.53±0.47 h for R; A C? of 864.88 ±309.15 ng-ml"1 for T and of 816.99±326.97 ngml1 for R; the relative bioavailability of T was 104.02%±20.88%. Statistic analysis showed T and R were bioequivalent preparations.Paired t-test was utilized to examine whether the datum and parameters obtained from the two methods mentioned above have significant difference: F (the relative bioavailability of T ), ke and t|/2( ke) did not differ between the two methods while Cmax, V and AUCa-t were quite distinct. Though several parameters in this paper were quite different between the two methods, the conclusion that when the standard substance couldn't be obtained in time, the new method using a relative standard substance as a substitute of the real standard substance to evaluate the bioequivalence of different drug preparations was rational and feasible could be justified.