Studies on the hypolipdemic and estrogenic activities of 2,8-dibenzylcyclooctanone and its analogues.
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Biomedical subjects
Publications and source records attributed to J Dubuc.
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The effect of clofibrate (CPIB) on lipid metabolism was studied in male rats rendered diabetic by intravenous injection of 80 mg/kg of streptozotocin. After 1 wk, the rats received by gastric intubation 242 mg/kg/day of CPIB for 7 days. Liver lipid concentration remained unchanged in experimental diabetes and after treatment with CPIB; however, due to decreased liver weight, total liver lipids were lower in diabetic rats. Elevation of cholesterol, phospholipids, and triglycerides in the serum of diabetic rats was reversed by CPIB treatment. Hepatic cholesterol synthesis in diabetic rats was suppressed to approximately 1/10 of that in normal rats. Treatment with CPIB abolished this residual cholesterogenic activity. Diabetes had no effect on intestinal cholesterol synthesis; a slight increase was noted after CPIB treatment. Basal and norepinephrine-induced lipolysis in fat pads was elevated in diabetic rats; CPIB had no effect on these changes. The data show that the elevated serum lipids in diabetic rats are lowered by treatment with C-IB. It was concluded that the hypocholesterolemic activity of clofibrate in rats is not caused by its suppression of hepatic cholesterol synthesis.
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Experiments have been carried out in dogs and man to determine the effect of hydrochlorothiazide (HCT) on the pharmacokinetics of propranolol and to evaluate the bioavailability of two dosage forms containing both propranolol and HCT (40/25 and 80/25 mg, respectively). In adult male beagles, 50 mg of HCT had no apparent effect on AUC, Cmax, Tmax, and T1/2 of propranolol administered concurrently. In man, INDERIDE (40/25 mg) and INDERIDE (80/25 mg) were shown to be similar in bioavailability to the reference formulations, i.e. the same amount of drugs administered as the separate tablets of INDERAL plus HYDRODIURIL.
Nineteen healthy male volunteers were given daily 160 mg propranolol hydrochloride in divided doses, either four 40-mg tablets or two 80-mg tablets, and the plasma propranolol concentration profiles were compared after one and seven consecutive days of drug administration. The results indicate that the relative rate and extent of propranolol absorption were greater after 80 mg given twice daily than after 40 mg given four times per day. Both differences were statistically significant at steady state attained with the seven-day treatment. The variability in the areas under the concentration-time curves of propranolol appeared to be smaller after the 80-mg twice-a-day dosing schedule. The results are in accordance with the observed therapeutic equivalence of the two dosing regimens.