کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5547602 1556143 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Excipient-mediated alteration in drug bioavailability in the rat depends on the sex of the animal
ترجمه فارسی عنوان
تغییرات متصل کننده توسط متصل کننده به مواد زیستی در موش صحرایی بستگی به جنس حیوانات دارد
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی

The pharmaceutical excipient, polyethylene glycol 400 (PEG 400), unexpectedly alters the bioavailability of the BCS class III drug ranitidine in a sex-dependent manner. As ranitidine is a substrate for the efflux transporter P-glycoprotein (P-gp), we hypothesized that the sex-related influence could be due to interactions between PEG 400 and P-gp. In this study, we tested this hypothesis by: i) measuring the influence of PEG 400 on the oral bioavailability of another P-gp substrate (ampicillin) and of a non-P-gp substrate (metformin); and ii) measuring the effect of PEG 400 on drug bioavailability in the presence of a P-gp inhibitor (cyclosporine A) in male and female rats. We found that PEG 400 significantly increased (p < 0.05) the bioavailability of ampicillin (the P-gp substrate) in male rats, but not in female ones. In contrast, PEG 400 had no influence on the bioavailability of the non-P-gp substrate, metformin in male or female rats. Inhibition of P-gp by oral pre-treatment with cyclosporine A increased the bioavailability of the P-gp substrates (ampicillin and ranitidine) in males and females (p < 0.05), and to a greater extent in males, but had no influence on the bioavailability of metformin in either male or female rats. These results prove the hypothesis that the sex-specific effect of PEG 400 on the bioavailability of certain drugs is due to the interaction of PEG 400 with the efflux transporter P-gp.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 107, 30 September 2017, Pages 249-255
نویسندگان
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