Studies On Pharmacokinetics Between Ranolazine Sustained Release Tablet In Beagle Dogs By HPLC

Chronic angina is one of the most common cardiovascular disorders known to impair quality of life and decrease life expectancy, in developing and developed countries. Though considerable progress has been made in the treatment of angina, many patients continue to experience the symptoms while a few remain refractory to conventional medications.Ranolazine selectively inhibits the late-sodium current which results in a reduced intracellular sodium and calcium overload during myocardial ischemia. This effect mediates a partial reduction in fatty acid oxidation (pFOX inhibitor) and consequent reciprocal increase in glucose oxidation during periods of myocardial stress. The increased glucose oxidation generates more adenosine triphosphate (ATP) per molecule of oxygen consumed.Objective To study bioequivalence between the Ranolazine sustained release tablet (test) and Ranolazine normal tablet(reference) by establishing HPLC method to determine Ranolazine in dog plasma.Methods The standard two-period 2×2 cross-over design was performed and 12 dogs were divided randomly into two groups. The plasma concentration of two Ranolazine formulations was determined by HPLC at scheduled time after a single oral dose (500 mg).Two-one sided test with 90% confidence interval(CI) was taken to evaluate the bioequivalence by 3P-37 statistical analysis software.Results Extracted with ethyl ether, the recovery of Ranolazine in plasma samples reached above 70%. HPLC method was applied with a C18 column and Berberine Hydrochloride was selected as internal standard. The mobile phase was ethyl-water(48:52, V:V)with the 1.0ml/min flow rate at 30℃temperature. The extracts were separated excellently and detected at 272 nm and the linear range of Ranolazine in plasma was 0.252～10.72μg/mL (r=0.9997).The 90% CI of AUC0～24h,Cmax,Tmax of the test were all between the range of 80%～125% of the reference.Conclusions HPLC method to determine plasma concentration of Ranolazine was accurate and sensitive.. The Ranolazine sustained release tablet(test)and normal(reference) were bioequivalent.