Effect of food on bioavailability of metronidazole from sugar-coated tablets having different dissolution rates in subjects with low gastric acidity

Abstract

The effect of food on the bioavailability of metronidazole from three commercial sugar-coated tablets varying markedly in drug dissolution behavior relative to pH was determined after oral administration in healthy male subjects with low gastric acidity. Four subjects, whose gastric acidities were evaluated as low (hypo- or anacidity) by using a non-intubation method (Gastrotest tablets administration method), received, in a cross-over fashion, a single 250 mg dose in sugar-coated tablet during periods of fasting and non-fasting. The tablet having the fastest and most pH-independent dissolution rate gave significantly higher Cmax and AUC0-32 than the other tablets having extremely slow dissolution at pH 5 or 7.2, when the drug was administered in the fasting state. However, there were no statistically significant differences in the above parameters among the tablets tested when they were administered postprandially. The improvement of the bioavailability of the tablets exhibiting poorer dissolution in the pH range of 5 to 7.2 is ascribed to suggestible vigorous agitation in the digestive tract stimulated by food intake.