Role of acetone bodies in the abnormal pharmacokinetic behavior of chlorpropamide in alloxan diabetic rabbits.

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Abstract
The effect of acetoacetic acid (AA) or .beta.-hydroxybutyric acid (HBA), each of which is a component of acetone bodies, on the pharmacokinetic behavior of chlorpropamide (CPA) was studied to elucidate the reason for the abnormal behavior of CPA was studied to elucidate the reason for the abnormal behavior of CPA under diabetic conditions. The serum level of CPA in the elimination phase showed a rapid and profound fall immediately after i.v. AA administration. A change of CPA distribution in the blood was observed in a normal rabbit. Under diabetic conditions, with high blood levels of acetone bodies, the effect of AA was temporary. A marked decrease of proximal tubular secretion of CPA was observed under normal conditions after the administration of AA. HBA showed effects similar to those of AA. A marked increase of CPA in red blood cells was observed in the presence of AA or HBA in normal rabbits. These results coincide with those obtained under diabetic conditions. The retardation of urinary excretion and the increase in CPA distribution into red blood cells in alloxan diabetic rabbits is mainly due to the presence of acetone bodies in the blood.

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