| In Vitro | In vitro activity: Clinofibrate is an antihyperlipidemic agent with IC50 with 40 μM on the activities of human liver 3α-hydroxysteroid dehydrogenases. Clinofibrate stimulates the activity of AKR 1C4 by 2.0-fold. The concentration of Clinofibrate at which maximum stimulation is achieved is 50 μM. |
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| In Vivo | Clinofibrate significantly decreases the high plasma cholesterol level of atherosclerotic rats, which is 823 +/- 256 (mean +/- SD) mg/dl, or about ten times that of control rats (85 +/- 11 mg/dl). On treatment with Clinofibrate, the cholesterol level is reduced mostly in the very low density lipoprotein (VLDL) fraction (d less than 1.006). Heparin-releasable lipoprotein lipase activity in epididymal adipose tissue, lipoprotein lipase activity in post heparin plasma, and VLDL-triolein hydrolizing activity in adipose tissue stromal vessels are higher in Clinofibrate-treated rats than in atherosclerotic rats. Of the enzymes in the arterial wall concerned with cholesterol ester metabolism, acid cholesterol esterase activity is decreased in atherosclerotic rats, and Clinofibrate treatment increased this activity. The ratio of acyl-CoA cholesterol acyltransferase activity (ACAT) to neutral cholesterol esterase activity is higher in atherosclerotic rats than in control rats and is lower in Clinofibrate-treated rats than in atherosclerotic rats. |
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| Animal model | Rats: Male Wistar rats weighing 100-160 g are used.
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| Formulation & Dosage | S-8527 and clofibrate are suspended in an appropriate amount of 5 gum arabic solution so that the daily dose would be 0.5 mL per 100 g of body weight. The drugs are given to the rats via stomach tube every a.m. for 7 days. Control groups are on an equal volume of vehicle. During the experimental period, the animals are fed on a commercial chow pellet ad libitum. About 24 hr after the last dose, the rats are anesthetized with ether and blood samples are obtained from the inferior venacava. After sacrifice, the livers are removed, washed with physiological saline, blotted on filter paper and weighed |
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| References | J Pharmacol Exp Ther. 1998 Jun;285(3):1096-103; Artery. 1983;12(3):145-55. |
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