کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2514980 1118495 2006 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of glyburide metabolites formed by hepatic and placental microsomes of humans and baboons
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Identification of glyburide metabolites formed by hepatic and placental microsomes of humans and baboons
چکیده انگلیسی

Glyburide (glibenclamide) is a second-generation sulfonylurea used for treatment of type-2 and gestational diabetes mellitus. To date, two glyburide metabolites have been identified in maternal urine: namely, 4-trans-hydroxycyclohexyl glyburide and 3-cis-hydroxycyclohexyl glyburide. The use of glyburide to treat gestational diabetes prompted us to investigate its metabolism by the placenta. The metabolism of glyburide by microsomal preparations from human and baboon placenta was compared with metabolism by their livers. The metabolites formed by the microsomes of the four tissues were identified by high-performance liquid chromatography–mass spectrometry using retention times, ion current (extracted at m/z 510), and selected-ion monitoring. The data obtained revealed the formation of six distinct hydroxylated derivatives of glyburide by each of the four microsomal preparations. However, the amounts of the six metabolites formed by the placentas were a fraction of that formed by the livers. Moreover, the relative quantities of each metabolite formed differed between species as well as between the two tissues. Also, the structure of the unidentified metabolites was determined by comparison with synthesized standards. These metabolites were identified as the 4-cis-hydroxycyclohexyl glyburide, 3-trans-hydroxycyclohexyl glyburide, and 2-trans-hydroxycyclohexyl glyburide. Therefore, one glyburide metabolite remains to be identified, but the data we obtained allowed us to suggest its structure.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 72, Issue 12, 15 December 2006, Pages 1730–1737
نویسندگان
, , , , , ,