Pharmacokinetic study of ranolazine in Chinese healthy volunteers / 中国药学杂志

ABSTRACT

OBJECTIVE: To study pharmacokinetics after administration of ranolazine sustained release tablets at a single and multiple dose to healthy Chinese volunteers. METHODS: This is a double-blind, random research. All volunteers were assigned to 7 cohorts according their enrollment sequence to receive ranolazine at dose levels of 500, 1000, 1500, 2000, 2500, 3000 mg; and one cohort has been given 500 mg ranolazine by multiple time. The plasma ranolazinecon centration was determined with a validated LC-MS/MS assay. RESULTS: The calibration curve was linear within the range of 5-4000 ng·mL-1. The LLOQ was 5 ng·mL-1 and RSDs of intra and inter day were less than 15%. After single dose, the main parameters in doses: 500, 1000, 1500, 2000, 2500, 3000 mgare: AUC0-t: (4876±1030), (9135±3796), (17562±8249), (14401±6848), (19410±10678), (26170±9896) ng·mL-1·h-1, respectively; MRT0-t: (10.17±1.94), (11.39±4.19), (12.35±3.87), (12.71±3.22), (8.39±3.16), (12.48±4.78) h, respectively; t1/2: (4.74±1.29), (5.35±2.21), (5.53±2.82), (8.64±5.22), (3.97±1.24), (11.64±6.40) h, respectively ;pmax: (471.78±132.84), (856.00±241.33), (1265.01±501.10), (1378.72±900.85), (1980.65±802.75), (3075.78±1516.90) ng·mL-1, respectively; CL: (106.34±24.33), (145.70±121.72), (103.29±48.25), (165.28±81.50), (158.69±77.85), (110.11±31.20) L·h-1, respectively; after the 1st dose in multiple dose, the parameters are: AUC0-t: (5593±4592) ng·mL-1·h-1, MRT0-t: (10.23±3.22) h, t1/2: (6.39±2.84) h, pmax: (527.42±340.15) ng·mL-1; CL: (155.19±133.14) L·h-1; after 106 dose, the parameters are: AUC0-t: (12318±7353) ng·nL-1 ·h-1; MRT0-∞: (11.56±2.14) h, t1/2: (5.11±1.19) h, pmax: (1007.78±455.95) ng·mL-1, pmin: (357.03±268.34) μg·mL-1, ρavg: (654.29±341.59) ng·mL-1, CLss: (82.89±50.42) L·h-1, Flu (109.04±29.93)%, accumulation: (1.25±0.12). There is no accumulation between single and multiple dose given. CONCLUSION: The main pharmacokinetics parameter of-anolazine in different doses we restudied in this research. Compared with the reference, the pharmacokinetics of this research is similar, vith the other study.