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 less than 0.001 versus baseline) and low-density lipoprotein cholesterol by 23% to 35% (p less than 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 less than 0.001 versus baseline), and low-density lipoprotein cholesterol was reduced by 47% to 56% (p less than 0.001). High-density lipoprotein cholesterol increased by 11% to 18% (p less than 0.05). Pravastatin was well tolerated; no clinical adverse events directly attributable to the drug were reported.
Pan
H Y
HY
Squibb Institute for Medical Research, Division of Medical Affairs, Princeton, NJ 08543-4000.
DeVault
A R
AR
Swites
B J
BJ
Whigan
D
D
Ivashkiv
E
E
Willard
D A
DA
Brescia
D
D
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002792:Cholestyramine Resin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D010743:Phospholipids / Q000097:blood; D017035:Pravastatin; D016032:Randomized Controlled Trials as Topic; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D009281:Naphthalenes; D010743:Phospholipids; D014280:Triglycerides; D002792:Cholestyramine Resin; D002784:Cholesterol; D017035:Pravastatin