J Clin Pharmacol
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The Journal of Clinical Pharmacology, 1974; 14:290-295
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Inhibition of Clofibrate-Induced Antidiuresis by Glybenclamide in Patients with Pituitary Diabetes Insipidus

János P. Radó M.D.1 and László Szende M.D.1

1 Isotopic Department and Metabolic Unit, János Hospital, XII. Diósárok ut 1. 1125 Budapest, Hungary.

Effects of clofibrate (Miscleron) and glybenclamide (Daonil) administered alone and in combination were studied on specific renal functions during ad libitum fluid intake in patients with pituitary diabetes insipidus.

Glybenclamide induced a significant increase in free water excretion in five patients with diabetes insipidus. On the other hand, in response to clofibrate, free water clearance decreased. A definite relationship was found between the clofibrate dose and the antidiuretic effect in two patients with diabetes insipidus. Concurrent administration of carbamazepine and clofibrate resulted in additive antidiuretic effects in one patient.

Administration of glybenclamide significantly inhibited the clofibrate-induced (and the clofibrate plus carbamazepineinduced) antidiuretic response.

The exact mechanism of the diuretic action of glybenclamide is unknown. A hypothesis is advanced according to which glybenclamide may inhibit a water-reabsorbing mechanism in the distal nephron independent of ADH.

Note:

The authors are deeply indebted to Dr. E. Feleky and the Hoechst A. G. (Frankfurt am Main) for the generous supplies of glybenclamide (Daonil) tablets.


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Copyright © 1974 by the American College of Clinical Pharmacology