Pharmacokinetics and pharmacodynamics of pravastatin alone and with cholestyramine in hypercholesterolemia

The pharmacokinetics, pharmacodynamics, and safety of pravastatin, a new selective 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor, were evaluated during monotherapy and with subsequent concomitant cholestyramine therapy in 33 patients with primary hypercholesterolemia in this randomized study. After 4 weeks, pravastatin monotherapy (5 mg, 10 mg, and 20 mg twice daily) significantly decreased total cholesterol by 17% to 24% ( p < 0.001 versus baseline) and low‐density lipoprotein cholesterol by 23% to 35% ( p < 0.001). High‐density lipoprotein cholesterol increased by 8% to 9%, and triglycerides decreased by 6% to 9%. The area under the serum concentration‐time curve and maximum serum concentration of pravastatin showed dose‐proportionality; time to maximum serum concentration and serum elimination half‐life were independent of dose. When added to pravastatin therapy, cholestyramine enhanced the lipid‐lowering effects of pravastatin. After 4 weeks of combination therapy, total cholesterol was reduced by 32% to 38% ( p < 0.001 versus baseline), and low‐density lipoprotein cholesterol was reduced by 47% to 56% ( p < 0.001). High‐density lipoprotein cholesterol increased by 11% to 18% ( p < 0.05). Pravastatin was well tolerated; no clinical adverse events directly attributable to the drug were reported. Clinical Pharmacology and Therapeutics (1990) 48, 201–207; doi: 10.1038/clpt.1990.136