Pravastatin: a new drug for the treatment of hypercholesterolemia.
The chemistry, pharmacology, pharmacokinetics, clinical trials, adverse effects, role in lipid-lowering therapy, and dosage and administration of pravastatin are reviewed. Pravastatin sodium is a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of hypercholesterolemia. Its structural formula is similar to those of lovastatin and simvastatin, but it is active in the parent form. It competitively inhibits HMG-CoA reductase, reduces hepatic cellular cholesterol synthesis, increases the expression of hepatic low-density lipoprotein (LDL) receptors, and reduces hepatic very low-density lipoprotein (VLDL) synthesis. Pravastatin has been demonstrated to reduce cholesterol in patients with familial and nonfamilial polygenic hypercholesterolemia and patients with diabetes mellitus. In doses of 10-40 mg/day, pravastatin has been shown to reduce total cholesterol by 15-30% and LDL cholesterol by 15-40%. It also increases high-density lipoprotein cholesterol by 2-20% and reduces triglycerides. It is generally well tolerated, with few adverse effects reported in clinical trials. Pravastatin reduces LDL cholesterol and increases HDL cholesterol comparably to lovastatin but possibly with fewer adverse effects. Further studies and clinical use will be needed to confirm potential differences in adverse effect profiles between the two drugs.
Jungnickel
P W
PW
University of Nebraska Medical Center, Omaha 68198-6045.
Cantral
K A
KA
Maloley
P A
PA
D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000188:drug therapy*; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy; D017035:Pravastatin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin