Effect of food and rosuvastatin on plasma mevalonic acid levels in male rats

Abstract

The present study determines the effect of food and rosuvastatin on plasma mevalonic acid (MVA) levels in rats. Single sample was taken under 12 h fasted and fed condition from 20 rats. Rats were divided into four groups (n=5). Rosuvastatin was dosed at 0, 3, 10, 30 mg/kg p.o prepared in 0.5% sodium carboxy methylcellulose (fasted condition). Sampling was carried out at predose, 0.25, 0.5, 1.5, 6, 16 and 24 h. Separated plasma samples were analysed by validated LC-MS/MS method. Data was processed using paired t test. WinNonlin software version 4.1 was used to calculate AUC_0-24h. MVA levels were significantly lower (43%) under fasting conditions as compared to fed conditions (p < 0.001). No diurnal variation in MVA levels was observed in all dose groups. AUC0-24h of MVA decreased by 30 to 35 % in 10 and 30 mg/kg dose groups (fasted condition), as compared to the control group. Plasma MVA levels in rats were decreased under fasting and also following rosuvastatin administration (under fasting). Thus, estimation of plasma MVA levels can be used to explore mechanism of statins and compare their efficacy in animal models. The use of MVA as a biomarker, however, for statin therapy needs to be investigated in man.

Keywords: rosuvastatin, plasma mevalonic acid, effect of food, animal models, LC-MS/MS

Ethiopian Pharmaceutical Journal Vol. 24, 2006: 59-64