Crilvastatin, a new drug from the pyrrolidone family, has been previously shown to inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in vitro and in vivo, to reduce the absorption of dietary cholesterol and to stimulate the activity of cholesterol 7 alpha-hydroxylase in the rat. The aim of this study was to evaluate the effects of crilvastatin on cholesterol and bile acid metabolism in the hamster. In hamsters fed on a lithogenic diet for 8 weeks, crilvastatin treatment (200 mg/day per kg body weight) did not change plasma lipid levels, failed to improve bile parameters and did not prevent gallstone formation. In hamsters fed on a basal cholesterol-rich (0.2%) diet for 8 weeks, crilvastatin at the same dose reduced the cholesterol level in the plasma by 20%, with a decrease of both low-density and high-density lipoprotein cholesterol. The drug did not significantly stimulate the biliary secretion of bile acids but significantly decreased the activity of acyl coenzyme A:cholesterol acyltransferase in the small intestine by 64%. This effect was enhanced when cholestyramine, a bile acid-sequestering resin, was given in combination with crilvastatin. Crilvastatin alone did not change the activity of cholesterol 7 alpha-hydroxylase in the liver, despite the marked reduction in both hepatic cholesterogenesis and intestinal absorption of dietary cholesterol (the absorption coefficient was 44 +/- 2% in treated hamsters vs. 61 +/- 7% in controls).

01 Aug 1996·British Journal of PharmacologyQ2 · MEDICINE

Differences in hypolipidaemic effects of two statins on Hep G2 cells or human hepatocytes in primary culture

Q2 · MEDICINE

Article

Author: Nicole Hasselot ; Nicolas Diaconescu ; Nicole Domingo ; Jean Philippe Rault ; Guy Jadot ; Françoise Chanussot ; Vincent Moutardier ; Thierry Clerc ; Véronique Sbarra ; Huguette Lafont ; Claude Laruelle

. The objective of this study was to compare in cultured human hepatocytes or Hep G2 cells, changes in the fate of unesterified low density lipoprotein (LDL)‐cholesterol induced by crilvastatin, a new cholesterol lowering drug and a reference statin, simvastatin.

. The experiments were carried out for 20 h, each well contained 4.2 × 105/cm2 Hep G2 cells or 0.5 × 105/cm2 human hepatocytes, 130 μm ursodeoxycholate, 0.68 μCi or 1.59 μCi unesterified human [14C]‐LDL‐cholesterol, crilvastatin or simvastatin at 0 or 50 μm (both cell types) or 300 μm (Hep‐G2 cells). Incubation with the two drugs resulted in increased amounts of unesterified [14C]‐LDL‐cholesterol taken by the two cell types, compared to control.

. Crilvastatin 50 μm led to significantly higher quantities of [14C]‐glyco‐ and [14C]‐tauro‐conjugated bile salts, compared to simvastatin. Statins reduced the apo B100 level secreted by the two cell types (simvastatin) or human hepatocytes (crilvastatin). Crilvastatin enhanced both the level of apo A1 secreted by the Hep G2 cells and the level of APF, a high density lipoprotein (HDL) and biliary apoprotein.

. Crilvastatin not only acts by stimulating LDL‐cholesterol uptake by hepatocytes, but also by enhancing the catabolism of LDL‐cholesterol in bile salts and probably by stimulating HDL and/or bile component secretion. Such a mechanism was not previously described for HMG CoA reductase inhibitors. Our results on APF show that this apoprotein could be considered also as an indicator of changes in bile and/or HDL compartments.

. The human hepatocyte model appeared to be a suitable and relevant model in the pharmacological***metabolic experiments carried out in this study. It led to more consistent data than those obtained with Hep G2 cells.

01 Nov 1995·European Journal of PharmacologyQ3 · MEDICINE

Crilvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, inhibits cholesterol absorption in genetically hypercholesterolemic rats

Q3 · MEDICINE

Article

Author: Jacqueline Férézou ; Claude Lutton ; Tahar Hajri ; Claude Laruelle

Crilvastatin is a new drug from the pyrrolidone family, which acts as a non-competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The long-term effects of oral crilvastatin treatment (200 mg per day per kg body weight for 4 and 10 weeks) were investigated on in vivo cholesterogenesis in male adult normocholesterolemic (SW) and genetically hypercholesterolemic (RICO) rats. In both strains of rats, the treatment had no effect on the plasma cholesterol level, but efficiently inhibited cholesterol synthesis in liver and intestine, as shown by the decreased incorporation of exogenous [14C]acetate into hepatic (3.5-fold in SW, 1.7-fold in RICO rats) and intestinal (2.5-fold in SW, 3.3-fold in RICO rats) sterols. In RICO rats in which the dietary cholesterol absorption coefficient was two-fold lower in treated (38%) than in untreated (78%) rats, this drug reduced intestinal cholesterol absorption. As a result, the total plasma cholesterol input (absorption + synthesis), measured by isotope analysis in RICO rats, was markedly lower in treated (11.3 mg per day) than in untreated animals (28.8 mg per day).

100 Deals associated with Crilvastatin

External Link

KEGG	Wiki	ATC	Drug Bank
D03601	-	-	-

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hyperlipidemias	Phase 2	-	Virbac SA	-
Hyperlipidemias	Phase 2	-	Panmedica SA	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis