Reference

Pharmacological comparison of the statins

Pharmacological comparison of the statins. Klotz, Ulrich (Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany). Arzneimittel-Forschung, 53(9), 605-611 (English) 2003 Editio Cantor Verlag. CODEN: ARZNAD. ISSN: 0004-4172. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. The statins (3-hydroxymethylglutaryl CoA (HMG-CoA) reductase inhibitors) represent drugs of first choice for treatment of hypercholesterolemia. The safety and efficacy of atorvastatin (CAS 134523-00-5), simvastatin (CAS 79902-63-9), lovastatin (CAS 75330-75-7), pravastatin (CAS 81093-37-0) and fluvastatin (CAS 93957-54-1) was well documented. Statins decrease dose-dependently low-d. lipoprotein (LDL) cholesterol as well as coronary events and total mortality. Clin. outcome data indicate that for simvastatin the lowest no. of treated patients is needed to prevent one major coronary event (NNT 15). Based on an approx. 30 % redn. of LDL (valid surrogate parameter) atorvastatin (5 mg/day) and simvastatin (10 mg/day) are the most potent agents whereas 40 mg of lovastatin or pravastatin and 60 mg of fluvastatin are needed to reach this "therapeutic target". While all statins share the same mode of action their pharmacokinetic properties and their susceptibility to drug interactions differ slightly. Agents inhibiting CYP3A4 (e.g. grapefruit juice, itraconazole, cyclosporine) should be discouraged if a patient is on atorvastatin, lovastatin or simvastatin. Likewise, fluconazole interferes with the CYP2C9-mediated hepatic elimination of fluvastatin. Moreover, coadministration of gemfibrozil should be avoided because it seems to increase the very low risk for statin-induced rhabdomyolysis. Several statins are available and their equieffective doses were defined. Selection of a particular drug should be primarily based on clin. outcome data. However, costs and in certain situations the pharmacokinetic profile including the interaction potential of the statins should be taken into account.

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.