Zheng-Kun Xia1, Yuan-Fu Gao2, Li-Ping Rong3, Xi-Qiang Dang4, Qian Shen5, Xiao-Yun Jiang3, Zhu-Wen Yi4, Hong Xu5. 1. Department of Pediatrics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. njxzk@126.com. 2. Department of Pediatrics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. 3. Department of Pediatrics, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. 4. Department of Pediatric Nephrology, Children's Medical Center, Second Xiangya Hospital, Central South University, Changsha 410011, China. 5. Department of Nephrology and Rheumatology, Children's Hospital of Fudan University, Shanghai 201102, China.
Abstract
BACKGROUND: Mizoribine (MZR) is an immunosuppressant used to treat adult nephropathy. There is little experience with the drug in treating Chinese children with frequently relapsing nephrotic syndrome (FRNS). We investigated the efficacy and safety for treating MZR with FRNS. Furthermore, the relationship between efficacy and serum concentration was investigated. METHODS: A prospective multicenter observational 12-month study was performed for evaluating the usefulness of MZR with FRNS. Serum MZR concentration was measured, and the relationships between pharmacokinetic parameters (Cmax, AUC), number of relapses, and urinary protein were evaluated. RESULTS: Eighty-two pediatric patients from four hospitals were treated with MZR and prednisone. MZR treatment significantly reduced the number of relapses and steroid doses. A correlation between pharmacokinetic parameters and relapses was observed, which fits well with the sigmoidal Emax model. Even in the relationship between pharmacokinetic parameters and urinary proteins, it was recognized that there was a threshold in the pharmacokinetic parameters for the therapeutic effect similar to the results obtained with the sigmoidal Emax model. Eleven patients (13.4%) experienced mild adverse events. CONCLUSIONS: MZR therapy was effective in reducing the number of relapses and steroid doses. No severe adverse reactions were observed. Therapeutically effective serum concentrations were estimated to be Cmax ≥ about 2 μg/mL or AUC ≥ about 10 μg h/mL. MZR and steroid treatment were effective and safe for pediatric FRNS.
BACKGROUND:Mizoribine (MZR) is an immunosuppressant used to treat adult nephropathy. There is little experience with the drug in treating Chinese children with frequently relapsing nephrotic syndrome (FRNS). We investigated the efficacy and safety for treating MZR with FRNS. Furthermore, the relationship between efficacy and serum concentration was investigated. METHODS: A prospective multicenter observational 12-month study was performed for evaluating the usefulness of MZR with FRNS. Serum MZR concentration was measured, and the relationships between pharmacokinetic parameters (Cmax, AUC), number of relapses, and urinary protein were evaluated. RESULTS: Eighty-two pediatric patients from four hospitals were treated with MZR and prednisone. MZR treatment significantly reduced the number of relapses and steroid doses. A correlation between pharmacokinetic parameters and relapses was observed, which fits well with the sigmoidal Emax model. Even in the relationship between pharmacokinetic parameters and urinary proteins, it was recognized that there was a threshold in the pharmacokinetic parameters for the therapeutic effect similar to the results obtained with the sigmoidal Emax model. Eleven patients (13.4%) experienced mild adverse events. CONCLUSIONS:MZR therapy was effective in reducing the number of relapses and steroid doses. No severe adverse reactions were observed. Therapeutically effective serum concentrations were estimated to be Cmax ≥ about 2 μg/mL or AUC ≥ about 10 μg h/mL. MZR and steroid treatment were effective and safe for pediatric FRNS.
Authors: K Yoshioka; Y Ohashi; T Sakai; H Ito; N Yoshikawa; H Nakamura; T Tanizawa; H Wada; S Maki Journal: Kidney Int Date: 2000-07 Impact factor: 10.612