Does the HMG-CoA reductase inhibitor pravastatin influence nucleation of cholesterol crystals in supersaturated model bile?
OBJECTIVE
To assess whether the presence in bile of HMG-CoA reductase inhibitors, which are secreted predominantly into the bile, influences biliary lithogenicity.


METHODS
Physiologic biliary concentrations of the hydrophilic HMG-CoA reductase inhibitor pravastatin were added to supersaturated model bile (cholesterol saturation index 1.4) and vesicles, the latter with and without the concomitant addition of the nucleation-promoting bile salt taurodeoxycholate.


METHODS
Nucleation time, defined as the number of days after which cholesterol monohydrate crystals are visible by phase contrast microscopy in filtered samples of model bile and vesicles, was assessed.


RESULTS
The addition of pravastatin 0.01-1 mg/ml did not influence the nucleation time of supersaturated model bile (mean nucleation time without pravastatin: 8.3 +/- 2.2 days (SD), with pravastatin 1 mg/ml 9.3 +/- 0.4 days and pravastatin 0.01 mg/ml 7.6 +/- 2.3 days). The addition of similar concentrations of pravastatin to vesicle fractions alone did not influence nucleation time (> 20 days), nor could it prevent the nucleation-promoting effect of taurodeoxycholate (nucleation time with or without pravastatin 1 day).


CONCLUSIONS
The results from this in-vitro study indicate that the presence of pravastatin in bile may not influence gallbladder bile lithogenicity. It can be hypothesized that this also applies to other HMG-CoA reductase inhibitors.
Smit
J W
JW
Department of Gastroenterology, University Hospital, Utrecht, The Netherlands.
Van Erpecum
K J
KJ
Gadella
M M
MM
Van de Heyning
B J
BJ
Van Berge-Henegouwen
G P
GP
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001646:Bile / Q000737:chemistry / Q000187:drug effects*; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D002769:Cholelithiasis / Q000737:chemistry / Q000209:etiology; D002784:Cholesterol / Q000737:chemistry*; D003460:Crystallization; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008858:Microscopy, Phase-Contrast; D017035:Pravastatin / Q000494:pharmacology*; D013657:Taurodeoxycholic Acid / Q000494:pharmacology; D013997:Time Factors
D000924:Anticholesteremic Agents; D002756:Cholagogues and Choleretics; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013657:Taurodeoxycholic Acid; D002784:Cholesterol; D017035:Pravastatin