EFFECTS OF SIMVASTATIN AND CHOLESTYRAMINE ON BILE LIPID-COMPOSITION AND GALL-BLADDER MOTILITY INPATIENTS WITH HYPERCHOLESTEROLEMIA

Although the effects of 3-hydroxy, 3-methylglutaryl coenzyme A (HMG-Co A) reductase inhibitors and bile acid sequestrants on bile lipid compo sition have been studied separately, no data are available on combinat ion therapy of these drugs. Moreover, the effects of prolonged (four w eeks) administration of these drugs on gall bladder motility, an impor tant determinant of cholesterol gall stone formation, have not been st udied so far. A prospective study was formed with eight patients hyper cholesterolaemia (age 53 (5) (SEM), body mass index 27.4 (1.1) kg m(-2 ), low density lipoprotein cholesterol 5.9 (0.3) mmol/l). They receive d treatment during three periods of four weeks with simvastatin 20 mg/ day, cholestyramine 4 g twice daily, and a combination of both in rand om order, each treatment period separated by a two week wash out perio d. Before treatment and after each treatment period, postprandial gall bladder motility was studied with ultrasound, followed by duodenal bi le sampling, Serum cholesterol decreased in all subjects in any treatm ent period illustrating good compliance. Molar percentages in duodenal bile of cholesterol, phospholipids, and bile salts were unchanged dur ing simvastatin and cholestyramine treatment. During combined therapy percentage bile salts was lower (72.5 (2.9)% v 77.8 (1.7)% at baseline , p<0.05) whereas phospholipids were higher (21.2 (2.4)% v 16.4 (1.3)% at baseline, p<0.05). As a result cholesterol saturation index (CSI) did not change in any treatment period. No cholesterol crystals were d etected in any bile sample, taken at baseline and after each treatment period. Bile salt hydrophobicity index during cholestyramine (0.19 (0 .02)) and combined treatment (0.22 (0.01)) decreased strongly compared with baseline (0.34 (0.01), p<0.001, p<0.01, respectively), resulting from increased proportions of glycocholate (59.4 (3.9)% (cholestyrami ne), 55.6 (2.4)% (combination), and 28.2 (2.2) (baseline), p<0.001)) a nd decreased proportions of deoxycholic acid and chenodeoxycholic acid . Fasting gall bladder volume was increased during simvastatin (28.7 ( 2.8) ml) v baseline (23.2 (2.3) ml, p<0.01) whereas, residual volume d id not differ (5.7 (0.9) ml (simvastatin) v 5.9 (0.7) (baseline). Duri ng cholestyramine and combined treatment, no significant differences i n gall bladder motility were seen. In conclusion, this study suggests that HMG-CoA reductase inhibitors alone and combined with cholestyrami ne do not affect major determinants of cholesterol gall stone formatio n, for example, CSI and gall bladder emptying. In addition cholestyram ine alone and combined with simvastatin leads to a strong decrease of bile salt hydrophobicity, which may be beneficial in the prevention of nucleation of cholesterol crystals.