SLOW ELIMINATION OF GLYBURIDE IN NIDDM SUBJECTS

OBJECTIVE - To determine the terminal elimination half-life of glyburi de in non-insulin-dependent diabetes mellitus (NIDDM) subjects after c essation of long-term treatment. RESEARCH DESIGN AND METHODS - Ten NID DM patients (5 of each sex, 36-72 years old, without hepatic or renal disease) talking a median glyburide dose of 14 mg/day, who were to sta rt insulin therapy because of sulfonylurea failure, were studied. Seru m glyburide concentrations, measured by a newly developed selective an d sensitive liquid chromatographic method, were followed from 10 to 48 h after the last glyburide dose. RESULTS - Serum glyburide levels dec lined in three different phases, with a terminal gamma-phase between 1 8 and 48 h having a mean +/- SD half-life of 15.0 +/- 6.7 h. Two patie nts had half-lives over 20 h. The half-life values did not correlate w ith fasting blood glucose, age, body weight, body mass index, or creat inine levels. The latter agrees with the assumption that glyburide is completely eliminated by metabolic transformation. Although longer tha n 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 slowe r than previously reported. The long half-life adds support to the use of a once- daily dosage of glyburide. It also justifies increased cau tion when using this sulfonylurea.