An exploring study on the pharmacodynamics of rosuvastatin in Chinese hypercholesterolemic patients

Abstract

Abstract: AIM: To develop a population pharmacodynamic (PPD) model for investigating the relationship between dose per kilogram body weight of rosuvastatin and LDL-C reduction in Chinese hypercholesterolemic patients.METHODS: Eligible patients were selected from relevant clinical trials and end point data were extracted for each patient. The primary efficacy end point was the mean percentage of change in LDL-C at 8 weeks from baseline. Potential covariates including trial, age, gender, body weight and baseline LDL-C levels were collected. Population modeling was performed with NONMEM. Bootstrap and Monte Carlo simulation was performed to assess the model robustness and prediction, respectively.RESULTS: Sigmoidal Emax model successfully described the dose-response relationship of rosuvastatin in Chinese hyperlipoidemic patients. The covariates did not significantly influence any hypercholesterolemic parameters. The population parameter estimates of E_max, ED₅₀ and gamma were 53.9%, 0.072 mg/kg and 3.76, and their relative standard errors were all small. Model robustness was validated by a nonparametric bootstrap. The 95% confidence interval of Monte Carlo simulation included about 50% patients' observed values of LDL-C reduction.CONCLUSION: This study developed a pharmacodynamic model for rosuvastatin in Chinese hypercholesterolemic patients with population method which described the pharmacodynamic characteristic of about 50% patients. The result indicates LDL-C reduction of rosuvastatin may be impacted by numerous factors except for dose, which should be investigated further.

Key words: Rosuvastatin, LDL-C reduction, Population pharmacodynamics, NONMEM

CLC Number:

R311

YANG Juan, LI Lu-jin, HE Ying-chun, XU Ling, LV Ying-hua, ZHANG Mi, LIU Hong-xia, ZHENG Qing-shan. An exploring study on the pharmacodynamics of rosuvastatin in Chinese hypercholesterolemic patients[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(8): 894-900.

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