Absorption of ranolazine in a rat model of in-situ single-pass intestine perfusion and the pharmacokinetics of its sustained-release tablets in Beagle dogs

Objective: To study the absorption characters of ranolazine at various concentrations in various intestine segments, and to compare the pharmacokinetic profile of the marketed abroad and domestic ranolazine sustained-release (SR) tablets in Beagle dogs. Methods: Phenol red was used as the indicator. The intestine absorption characters of ranolazine were detected by the in-situ method of single-pass intestine perfusion. The concentration of phenol red or ranolazine was determined by HPLC. Either abroad (reference) or domestic (test) ranolazine SR tablets (500 mg) were randomly administered with a single crossover design in 6 Beagle dogs. The plasma concentration of ranolazine was measured by HPLC. The pharmacokinetic parameters were estimated with a BAPP 3.0 program. Results: There was no significant difference in the appearance permeability (P_app) or K_a between various intestine segments under various concentrations (P > 0.05). The relative bioavailability of the test tablets in Beagle dogs was (104.5 ± 30.1)%. Conclusion: Ranolazine is absorbed mainly by passive diffusion mechanism. The concentration-time curve of the domestic ranolazine SR tablets is similar to that of abroad tablets, and there is no dumping-dose after a single dose administration.