EFFECTS OF PRAVASTATIN ON PLASMA AND URINARY MEVALONATE CONCENTRATIONS IN SUBJECTS WITH FAMILIAL HYPERCHOLESTEROLEMIA - A COMPARISON OF MORNING AND EVENING ADMINISTRATION

In order to determine whether there is a difference in the effect of t he hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor p ravastatin on cholesterol synthesis between the morning and the evenin g, we studied the 24-h profile of mevalonate in plasma and urine in 11 subjects with heterozygous familial hypercholesterolaemia. In study 1 , eight subjects with familial hypercholesterolaemia took pravastatin (20 mg) once in the morning, and another 20-mg dose in the evening aft er a 1-week wash-out period. In study 2, five subjects with familial h ypercholesterolaemia took pravastatin (20 mg per day) in the morning o n 3 consecutive days and on 3 days in the evening after a 1 day wash-o ut. Plasma mevalonate concentrations were reduced at 9 h and 5 h after pravastatin administration in the morning and the evening, respective ly. Urinary mevalonate excretion was significantly reduced at 4-8 h af ter pravastatin administration in the morning (51 vs 19 nmol . h(-1)) and at 4-16 h after pravastatin administration in the evening (56 vs 2 7 nmol . h(-1)). Daily urinary mevalonate excretion was equally and si gnificantly reduced by pravastatin in the morning or evening. In concl usion, we found that morning and evening administration of pravastatin caused equal reductions in plasma and urinary mevalonate concentratio ns.