Effects of pravastatin and ursodeoxycholic acid on cholesterol and bile acid metabolism in patients with cholesterol gallstones.
To investigate the effects of pravastatin and ursodeoxycholic acid (UDCA) on cholesterol and bile acid metabolism in humans, 41 patients with cholesterol gallstone disease were allocated to four groups and treated with pravastatin (20 mg/day), UDCA (600 mg/day), both pravastatin and UDCA, or neither drug (control) for 1-2 weeks prior to elective cholecystectomy. Cholesterol 7 alpha-hydroxylase activity and serum levels of total 7 alpha-hydroxycholesterol were significantly increased by pravastatin and unaffected by UDCA. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was markedly increased by pravastatin and decreased by UDCA. UDCA significantly decreased biliary cholesterol concentration and the cholesterol saturation index and prolonged the nucleation time; however, pravastatin alone had little effect on biliary lithogenicity. Serum total and low-density lipoprotein (LDL)-cholesterol levels were reduced most by the combined administration of pravastatin and UDCA. In conclusion, at a dose of 20 mg/day, pravastatin increased bile acid synthesis but did not decrease biliary lithogenicity. UDCA had no significant effect on bile acid synthesis, but markedly decreased biliary lithogenicity.
Okamoto
S
S
First Department of Surgery, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Nakano
K
K
Kosahara
K
K
Kishinaka
M
M
Oda
H
H
Ichimiya
H
H
Chijiiwa
K
K
Kuroki
S
S
D000328:Adult; D000368:Aged; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D002769:Cholelithiasis / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D003460:Crystallization; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology*; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D017035:Pravastatin