Reference

Triglyceride-lowering effect of pitavastatin in a guinea pig model of postprandial lipemia

Triglyceride-lowering effect of pitavastatin in a guinea pig model of postprandial lipemia. Aokia, Taro; Yamazakia, Hiroyuki; Tamakia, Taro; Sato, Fumiyasu; Kitahara, Masaki; Saito, Yasushi (Tokyo New Drug Research Laboratories I, Atherosclerosis Research Department, Pharmacology Group, Kowa Company, Ltd., Tokyo 189-0022, Japan). Arzneimittel-Forschung, 53(3), 154-158 (English) 2003 Editio Cantor Verlag. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The triglyceride (TG)-lowering effect of pitavastatin (CAS 147526-32-7), a potent 3-hydroxy-3-methylglutaryl-CoA (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 max. 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 equiv. for pitavastatin and atorvastatin, but weaker with simvastatin. 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 chylomicron (CM)-TG in the small intestine, and the activity of lipoprotein lipase (LPL), which is the hydrolysis enzyme of the very low d. lipoprotein (VLDL)-TG and CM-TG, was examd. 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 d. lipoprotein (LDL) receptor. This effect is expected to improve postprandial lipemia.

Bioequivalence study of two formulations of simvastatin tablets in healthy Thai volunteers

Bioequivalence study of two formulations of simvastatin tablets in healthy Thai volunteers. Lohitnavy, Manupat; Lohitnavy, Ornrat; Chaijittiprasert, Kasinee; Taytiwat, Prawit; Polnok, Sanglar (Bioequivalence Test Center, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand). Arzneimittel Forschung, 54(1), 31-34 (English) 2004 Editio Cantor Verlag. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 63 The bioequivalence of 2 formulations of 10 mg tablets of simvastatin (CAS 79902-63-9), Vascor as test and a com. available prepn. as ref., in 18 healthy Thai male volunteers was assessed. In a randomized, single dose, 2-period, crossover study design with a 1-wk wash-out period, each subject received 4 tablets of 10-mg simvastatin tablets. Blood plasma samples were collected over a 24-h period after administration. Subsequently, plasma concns. of simvastatin and its hydroxy acid metabolite were analyzed by LC/MS/MS. Pharmacokinetic parameters were detd. by non-compartmental anal. The results showed that 90% confidence intervals of the peak concn. (Cmax) and the area under the concn.-time curve (AUC) of simvastatin and its hydroxy acid metabolite of ref. and test were within 80 %-125 %. Consequently the bioequivalence of these 2 prepns. can be concluded.