The Antidiabetic Effect and Pharmacokinetic Properties of Glipizide

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Abstract
In 13 patients with maturity-onset diabetes mellitus which did not respond to diet therapy alone, serum concentration of glipizide, blood glucose (B-G) concentration, serum immunoreacitve insulin (S-IRI) and plasma glycerol (P-G) were monitored hourly over 12 h after placebo, an initial dose of glipizide (5 mg/orally) and long-term treatment with glipizide (range 7.5-20 mg, mean 10.4), which produced fasting B-G of less than 8 mmol/l. During the long-term treatment, glipizide was given in a random, crossover pattern, either as a single dose in the morning or as a 3-part divided dose regime, in the same total daily amount. The duration of the immediate effects of glipizide on B-G, S-IRI and S-IRI/B-G was 9, 4.5 and 6.5 h, respectively. The mean apparent half-life of glipizide was 4.1 h, the mean distribution volume 0.13 l/kg and the mean plasma clearance 0.023 l/kg .times. h. The area under the concentration curve from 0730 to 1930 h was 15% higher after the single dose regime. The serum levels of glipizide at 10 h were only 30% lower than after the 3-part divided sode regime. There were no significant differences between the single and divided dose regimes as regards B-G, S-IRI and S-IRI/B-G, although the mean B-G for the 12 h period was somewhat lower after the former than after the latter (7.0 against 8.7 mmol/l).