Triglyceride-lowering effect of pitavastatin [corrected] in a rat model of postprandial lipemia.
The triglyceride-lowering effect of pitavastatin, a potent 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, was investigated in a rat model of postprandial lipemia. Plasma triglyceride levels started to increase 4 h after the fat load, reached the maximum at 6 h and then gradually decreased. A single dose of pitavastatin (1 mg/kg) significantly suppressed chylomicron-triglyceride secretion into the lymph by 40% and delayed the elevation of plasma triglyceride. Pitavastatin at 1 mg/kg decreased the 6-h plasma triglyceride levels by 53% and at 0.5 mg/kg decreased the 0-12 h area under the curve (AUC) of triglyceride levels by 56%. Atorvastatin also caused decreases, but to a lesser extent. Pitavastatin, and atorvastatin to a lesser extent, reduced the activity of the intestinal microsomal triglyceride transfer protein (MTP) at 6 h. These results suggested that a single dose of pitavastatin lowered postprandial triglyceride levels in rats by decreasing chylomicron-triglyceride secretion, probably through a reduction of intestinal MTP activity and triglyceride droplet formation in the endoplasmic reticulum.
Tokyo Research Laboratories, Pharmaceutical Division, Kowa Company, Ltd., 2-17-43, Higashimurayama, Tokyo, 189-0022, Japan. t-oaki@kowa.co.jp
Taro
T
Aoki
Yasunobu
Y
Yoshinaka
Hiroyuki
H
Yamazaki
Hideo
H
Suzuki
Taro
T
Tamaki
Fumiyasu
F
Sato
Masaki
M
Kitahara
Yasushi
Y
Saito
D000818:Animals; D002914:Chylomicrons / Q000187:drug effects; D006949:Hyperlipidemias / Q000188:drug therapy*; D008297:Male; D019518:Postprandial Period; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood*
D002914:Chylomicrons; D011804:Quinolines; D014280:Triglycerides; C108475:pitavastatin