Population Pharmacokinetic Analysis of Mizoribine in Chinese Renal Transplant Recipients

作者：Liu, L.; Ren, B.; Zhang, H.; Li, J.; Fu, Q.; Jiang, J.; Deng, S.; Qiu, J.; Chen, G.; Fei, J.; Chen, L.; Wang, C.^*

来源：Transplantation Proceedings, 2018, 50(8): 2392-2397.

DOI：10.1016/j.transproceed.2018.03.030

• PULSE THERAPY
• MYCOPHENOLATE-MOFETIL
• NEPHROTIC SYNDROME
• LUPUS NEPHRITIS
• EFFICACY
• BREDININ
• CYCLOSPORINE
• ACTIVATION
• MECHANISM
• CELLS

Background. We calculated the population pharmacokinetics of mizoribine in adult Chinese patients and compared the parameters with those of Japanese patients to determine whether there are any ethnic differences in blood concentration transition between these 2 populations. @@@ Methods. The blood concentrations of mizoribine in 21 Chinese patients who were administered mizoribine after renal transplantation were measured at 304 time points. The absorption lag time, absorption rate constant, apparent distribution volume, and oral clearance were thereafter calculated and compared with the respective Japanese references. @@@ Results. The absorption lag time, absorption rate constant, and apparent distribution volume calculated in this study were, respectively, 0.353 hour, 0.856 hour-1, and 0.776 L/kg. The oral clearance was calculated as 2.18 times the creatinine clearance using creatinine clearance as a function. The absorption rate constant, apparent distribution volume, and oral clearance are determinants of the maximum blood concentration, trough, and area under the blood concentration time curve. The relative absorption rate constant, apparent distribution volume, and oral clearance were 0.9-, 0.9-, and 1.2-fold, respectively, in Chinese patients compared with those in Japanese patients. These values are within the confidence limit, suggesting that there is no significant PK difference between the 2 ethnic groups. @@@ Conclusions. Results of this study showed no ethnic difference in blood mizoribine concentration transition between Chinese and Japanese patients. In addition, the population pharmacokinetic parameters obtained in this study are useful in determining the initial dosage or in the Bayesian analysis of mizoribine concentrations using scarce time points.

• 出版日期2018-10
• 单位中山大学