INFLUENCE OF MEALS ON THE BIOAVAILABILITY AND PHARMACOKINETIC PROFILES OF CHLORPROPAMIDE IN MAN

INFLUENCE OF MEALS ON THE BIOAVAILABILITY AND PHARMACOKINETIC PROFILES OF CHLORPROPAMIDE IN MAN

Abstract:

The effects of three different Nigerian meals on the bioavailability and pharmacokinetic profiles of chlorpropamide were studied in healthy subjects and in freshly diagnosed Type II diabetic patients. The batch of chlorpropamide tablets and the meals used were pre—analyzed using official methods- The tablets complied with the B.P. (1988) requirements stated under the monograph for chlorpropamide and the meals contained high carbohydrate contents of 80.5%, 76.0% and 84.5% for maize, cassava and yam flour meals respectively. Plasma levels of chlorpropamide were determined using HPLC method. In addition, glucose levels were measured by a standard glucose oxidase method (Martinek, 1964). Higher levels of chlorpropamide were observed when the drug was administered in fasting state compared with concomitant administration of drug with maize, and cassava flour meals. Concomitant administration of the drug with yam flour meal however increased chlorpropamide levels in healthy subjects and had no effect on chlorpropamide levels in diabetic patients. Significantly lowered postprandial plasma glucose increments were observed when 250mg chlorpropamide tablet was taken with each meal than when each meal was taken alone, and the glucose levels were even lowered when the drug was taken 30min prior to meal ingestion compared with when the drug was taken concomitantly with each meal. No significant postprandial plasma glucose increments were observed in healthy subjects. The pharmacokinetic parameters were calculated by a computer programme KINEMP1 Administration of chlorpropamide concomitantly with each meal compared with the fasting state affected some absorption parameters (lagtime, tmax, Cmax, ka and tl/2x), the extent of absorption, volume of distribution and the elimination parameters calculated in this study were not significantly affected by any of the meals. Some pharmacokinetic parameters (lagtime, Cmax, tmax, ka, tl/2x and Vd) calculated for the healthy subjects and diabetic patients were significantly different. There was a relationship between the hypoglycaemic responses and chlorpropamide levels attained after administration of the drug to healthy volunteers but no direct relationship was found for the patients. Lower and statistically significant levels of chlorpropamide were detected in saliva compared with the plasma. The saliva and plasma (S/P) ratio was less than unity at each sampling point and there was a correlation between the saliva and plasma concentratons of chlorpropamide measured.

INFLUENCE OF MEALS ON THE BIOAVAILABILITY AND PHARMACOKINETIC PROFILES OF CHLORPROPAMIDE IN MAN