Sex-Linked Blood-Glucose Pattern in Rats Under Varying Test Conditions

Abstract

A difference of reaction patterns in female and in male rats was found to exist and was statistically ascertained by shortterm tests, with respect to the changes in glucose metabolism after a single dose of HB 419 (Glibenclamide). The test methods as reported in this study were designed to yield information on whether and to what extent modifications of maintenance conditions, different levels of drug dosage, various methods of administration, and long-term treatment conditions, will exert influences on this variance of metabolic patterns. These test series were carried out with a total of 194 female and male Sprague-Dawley rats; the results are the following:
Regardless of maintenance conditions, methods of administration, choice of dosage, or period of administration, a difference exists between female and male rats in terms of metabolization of the lipoid-soluble sulfonylurea HB 419; which difference has been ascertained by statistical methods for the sex factor as well as for the time factor and for the correlation between these two factors. This difference in patterns between the sexes in rats which has been ascertained in short-term tests also with varying dosages, was further confirmed by the results of long-term tests at varying application methods of the drug, to the exclusion of any adaptation, activation, or exhaustion symptoms of the hepatic microsomal enzymes responsible for oxidative metabolization.

In dependence of maintenance conditions, methods of administration, choice of dosage, and period of administration, test-linked phase displacements and dosage-linked differences of glucose depression only have been observed, which are being discussed and which are found to be sex-independent.

These differences hitherto largely neglected - between female and male rats in terms of metabolization patterns of lipoid-soluble sulfonylurea substances, offer suitable explanations of variances in results and interpretations of investigations.

Key words

Blood Glucose Male Rat - Female Rat - Glibenclamide