title: Triglyceride-lowering effect of pitavastatin in a guinea pig model of postprandial lipemia.
abstract: The triglyceride (TG)-lowering effect of pitavastatin (CAS 147526-32-7), a potent 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, was investigated in a guinea pig model of post-prandial lipemia. Plasma TG levels started to rise 2 h after the fat load, reached the maximum at 8 h and then gradually decreased. A 14-day dose of pitavastatin at 3 mg/kg decreased the 8 h plasma TG levels by 59%, and the 0-12 h area under the curve (AUC) of TG levels above the initial levels, by 77%. This effect was also shown with 30 mg/kg of atorvastatin (CAS 134523-00-5), and the same dose of simvastatin (CAS 79902-63-9). The intensity of the action was equivalent for pitavastatin and atorvastatin, but weaker with simvastatin. In order to clarify the mechanism of this action, the effect of pitavastatin exerted on the activity of microsomal triglyceride transfer protein (MTP), which participates in the secretion to the lymph vessel of chyromicron (CM)-TG in the small intestine, and the activity of lipoprotein lipase (LPL), which is the hydrolysis enzyme of the very low density lipoprotein (VLDL)-TG and CM-TG, was examined. However, an influence on the activity of MTP or LPL by pitavastatin was not shown. These results suggested that pitavastatin lowered the postprandial TG levels in guinea pigs by accelerating the remnant clearance, probably through the enhancement of the low density lipoprotein (LDL) receptor. This effect is expected to improve postprandial lipemia.
authors.affiliation: Tokyo New Drug Research Laboratories I, Atherosclerosis Research Department, Pharmacology Group, Kowa Company, Ltd., Tokyo, Japan. t-aoki@kowa.co.jp
authors.forename: Taro
authors.initials: T
authors.lastname: Aoki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Taro
authors.initials: T
authors.lastname: Tamaki
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Sato
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitahara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000069059:Atorvastatin; D002352:Carrier Proteins / Q000378:metabolism; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D000960:Hypolipidemic Agents; D007413:Intestinal Mucosa / Q000378:metabolism; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D019518:Postprandial Period / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D019821:Simvastatin / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood*
chemical_list: D000925:Anticoagulants; D002352:Carrier Proteins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008055:Lipids; D008074:Lipoproteins; D011758:Pyrroles; D011804:Quinolines; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D006493:Heparin; D000069059:Atorvastatin; D019821:Simvastatin; C108475:pitavastatin