290 The Journal of Clinical Pharmacology Inhibition of Clofibrate-Induced Antidiuresis by Glybenclamide in Patients with Pituitary Diabetes Insipidus JANOS P. RAD6. M.D.. and LASZLO SZENDE. M.D. Budapest, Hungary G LYBENCLAMIDE, a new potent hypo- glyceinic sulfonylurea drug, was re- ported to have unexpected diuretic action in patients with pituitary diabetes in- sipidus (PDI) 1,2 Chlorpropamide, the older sulfonylurea compound, has been shown to exert an antidiuretic effect,34 by increasing the release of ADH from the posterior pituitary and by enhancing its peripheral action.5 Similar antidiuretic action was reported with carbamazepine6’7 and clofibrate,8 which also act by increas- ing the release of ADH from the neuro- hypophysis. It was speculated2 that “vaso- pressin-like” agents (chlorpropamide, carbamazepine, and clofibrate) and gly- benclamide may have an opposite central and/or peripheral (renal) action. There- fore, we decided to investigate the sup- posed antagonistic action of clofibrate and glybenclamide. It was found that gly- benclamide significantly inhibited the clofibrate-induced antidiuresis in patients with PDI. Materials and Methods Seven patients with PDI were investi- gated. The diagnosis was established by serum and urine osmolality measurements, From the Isotopic Department and Metabolic Unit, J#{225}nosHospital, XII. Di#{243}s#{225}rok ut 1. 1125 Budapest, Hungary. water deprivation test, and the modified Carter-Robbins test.91#{176} Free water clear- ance and glomerular filtration rate were measured throughout the Carter-Robbins test. The patients were not restricted to bed, but were not allowed to leave the ward. They were kept on the usual hospital diet allowing water ad libitum. In each pa- tient urine was collected daily for creatinine level and osmolality measure- ments during the entire control and treat- ment periods. Fasting serum osmolality was measured at 8 A.M. Drugs were given by mouth. After an adequate control period (3-14 days), 20 ing glybenclamide (Daonil, Hoechst) was administered daily during 3-11 days to five patients with PDI. Data of 32 treatment days were compared with those of 35 control days. The effects of clofibrate (Miscleron, Chinoin) and clofibrate plus glybenclam- ide were studied in two patients with PDI. Clofibrate was administered in doses of 500, 1000, and 2000 mg per day; 1000 and 2000 mg clofibrate were administered concurrently with glybenclamide. Gly- benclamide, 10 mg per day, was given to patient 1, and 30 mg per day, to patient 2. The entire experimental protocol can be seen in Figs. 2 and 3, with the excep-