Tissue selectivity of the cholesterol-lowering agents lovastatin, simvastatin and pravastatin in rats in vivo.
Tissue selectivity of lovastatin, simvastatin and pravastatin was determined in male rats. Peak levels of active drug were found in all tissues examined between 0.5 and 2 hours after oral administration. The area under the curve describing 24 hour exposure of the tissues to drug indicated that the drugs were preferentially concentrated in the liver. However, the concentration of pravastatin was approximately 50% that of either lovastatin or simvastatin in the liver and 3-6 times higher in peripheral tissues. These studies demonstrate that the hydrophobic prodrugs, lovastatin and simvastatin show greater selectivity than the hydrophilic agent pravastatin towards the liver which is the target organ for inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.
Germershausen
J I
JI
Merck Sharp & Dohme Research Laboratories Rahway, New Jersey 07065.
Hunt
V M
VM
Bostedor
R G
RG
Bailey
P J
PJ
Karkas
J D
JD
Alberts
A W
AW
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism; D006538:Heptanoic Acids / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008297:Male; D009281:Naphthalenes / Q000493:pharmacokinetics*; D017035:Pravastatin; D051381:Rats; D019821:Simvastatin; D013154:Spleen / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin