Clinofibrate is a new hypelipidemic agent and a competitive hydroxymethylglutaryl coenzyme A reductase with an IC50 of 0.47 mM. Clinofibrate is a derivative of clofibrate. Clinofibrate, as a antihyperlipidemic drug, activiates human liver 3alpha-hydroxysteroid dehydrogenase. The optimal pha of activation this enzyme by the compound clinofibrate was about 7.5. The concentrations giving maximum stimulation (1.8 to 2.4 fold) for clinofibrate were 50 μM. The activation by the antihyperlipidemic drug, clinofibrate, elevated both Km and Kcat (turnover number) values for the coenzyme and substrates. Clinofibrate lacks the chloro group, methyl goup on the alpha-carbon or carboxyl group. Thus, clinofibrate greatly decreased the stimulatory effects. Kinetic analysis with respect to NAPD+ exhibited that clinofibrate was nonessential activators with dissociation constants of 6 μM. These data suggest that the long-term treatment with the antihyperlipidemic drugs generates effects on the metabolism of steroid hormones and bile acids, as well as several-containing drugs mediated by the enzyme.
||Seven-week-old Sprague-Dawley rats (SLC), six-week-old ICR-SLC mice and a one-year-old beagle dog
||Administered orally or intravenously
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
|Body Surface Area (m2)
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by
||Animal B Km
|Animal A Km
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
||DMSO 90 mg/mL