کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5809717 | 1556165 | 2016 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Sex-by-formulation interaction assessed through a bioequivalence study of efavirenz tablets Sex-by-formulation interaction assessed through a bioequivalence study of efavirenz tablets](/preview/png/5809717.png)
Although sex-related differences in gastrointestinal physiology have been vastly reported, its impact on drug oral bioavailability and bioequivalence (product discrimination) is often ignored. On this work results from an average bioequivalence study between tablets containing 600Â mg of the antiretroviral efavirenz (EFV), carried out with 14 healthy subjects (8 female and 6 men) in a randomized 2-period, 2-treatment crossover design, are analyzed from a sex-based approach. Sequences were balanced within each sex group. Considering all subjects, no differences were observed on EFV absorbed amount, as shown by the estimated 90CI of the AUC96 Test/Reference bioequivalence ratio (T/R): 0.950-1.05. However, results were not conclusive due to the 90CI for CMAX T/R was 0.743-1.07. Over this parameter, a significant sex-by-formulation interaction was detected: 90CI CMAX T/R was 0.838-1.36 in women and 0.540-0.920 in men; with a 52% relative difference between point estimates. Formulation differences were therefore evidenced only by male subjects. In vitro dissolution and disintegration tests for both products were carried out in two aqueous media: A) SLS 0.25% and B) HCl/KCl pHÂ 1.2. T/R results for dissolution efficiency and tablet disintegration times of formulations in both A and B media were highly correlated with CMAX T/R bioequivalence results observed in women and men respectively, showing that a dissimilar gastrointestinal environment between sexes affected EFV oral absorption. This work shows how sex-by-formulation interaction can affect bioequivalence conclusions. Sex effect on product discrimination should be specially disclosed in bioequivalence studies, mainly for drugs aimed to be given to both sexes.
59
Journal: European Journal of Pharmaceutical Sciences - Volume 85, 31 March 2016, Pages 106-111