RESUMEN
Bioavailability study was conducted on 250 mg-chlorpropamide tablets from 10 locally manufactured brands and an innovator one (Diabinese). The results of the tests for quality according to the pharmacopoeia were as follows: weight uniformity of all the brands was in accordance with the USP XXII standard, the content of one of them failed, and disintegration test of one brand failed (BP 1,973 and USP XIX). In addition five brands failed to meet the USP XXII dissolution specification, while only 2 brands failed to meet the BP 1,988 specification. Four brands of chlorpropamide tablets were selected for studying their bioequivalence in 20 Thai healthy male volunteers, receiving orally a half dose of 250 mg, using a cross-over randomized design, one representing the rapid dissolution rate group, the innovator one representing the intermediate dissolution rate group and 2 brands representing the slow rate group (one failed the USP XXII, but met the BP 1,900 dissolution specification (a) and the other failed both USP XXII and BP 1,988 dissolution specification (b). Plasma chlorpropamide levels were determined by a specific high performance liquid chromatographic method. Individual plasma profiles were analysed using PC NONLIN computer program-two compartment open model. There was no significant difference (p > 0.05) with regard to extent and rte of absorption between the brand having the intermediate dissolution rate (the innovator one) and the slow dissolution drug (b), while the brand representing rapid dissolution rate was absorbed more rapidly (p < 0.05). However the absorption rate of the local made product had an higher standard error than that of the innovator, absorption rates did not have any effect on the hypoglycemia, because drug levels in the absorption period were lower that the therapeutic level and steady state. Besides, in testing blood glucose level of volunteers before and after having received orally the 4 brands at different times, it was fond that there was no significant difference (p > 0.05) between the level before taking the drugs and that after 2 hours. There was no significant correlation between the in vivo absorption rate and the dissolution, USP XXII method (p > 0.05). The mean peak chlorpropamide concentration in plasma (half dose taken) was between 14.59 and 16.69 ug/ml, and the half-life (T1/2, e) was between 43.73 and 49.42 hours.