Slow Elimination of Glyburide in NIDDM Subjects

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Abstract
OBJECTIVE To determine the terminal elimination half-life of glyburide in non-insulin-dependent diabetes mellitus (NIDDM) subjects after cessation of long-term treatment. RESEARCH DESIGN AND METHODS Ten NIDDM patients (5 of each sex, 36-72 years old, without hepatic or renal disease) taking a median glyburide dose of 14 mg/day, who were to start insulin therapy because of sulfonylurea failure, were studied. Serum glyburide concentrations, measured by a newly developed selective and sensitive liquid chromatographic method, were followed from 10 to 48 h after the last glyburide dose. RESULTS Serum glyburide levels declined in three different phases, with a terminal 7-phase between 18 and 48 h having a mean ± SD half-life of 15.0 ± 6.7 h. Two patients had half-lives over 20 h. The half-life values did not correlate with fasting blood glucose, age, body weight, body mass index, or creatinine levels. The latter agrees with the assumption that glyburide is completely eliminated by metabolic transformation. Although longer than previously observed, the current half-life values are in accordance with clinical experience that glyburide is a long-acting sulfonylurea. CONCLUSIONS The elimination of glyburide in NIDDM subjects is slower than previously reported. The long half-life adds support to the use of a once-daily dosage of glyburide. It also justifies increased caution when using this sulfonylurea.

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