The pharmacokinetics of metformin: a comparison of the properties of a rapid-release and a sustained-release preparation.
1983
: The pharmacokinetic differences between a rapid-release metformin preparation of 500 mg (RRM) and a sustained-release metformin preparation of 500 mg (SRM), whose gastrointestinal side effects may be less, were compared after a single dose and after continuous 5-day use during a steady-state phase. In the single-dose trial the mean peak serum level of 1.00 micrograms/ml from RRM and 0.61 micrograms/ml from SRM were reached at 3 h, and at 3 and 4 h, respectively, after ingestion of the drugs. Serum metformin levels from RRM were consistently higher up to 8 h, and the AUC0-8h value for RRM was from 4.25 and 2.49 for SRM (p less than 0.001). Over a 24-h period 40% of the given dose was recovered in urine from RRM. The value for SRM was 25%. The elimination half-life was 2.0 h for RRM and 2.6 h for SRM. During the steady-state trial the mean basal serum metformin concentration was higher after SRM (0.33 micrograms/ml) than after RRM (0.20 micrograms/ml), although the mean peak serum metformin level remained lower after SRM. On the 5th day the AUC0-8h values obtained after RRM and SRM were comparable (6.88 vs 6.59; N.S.).
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