Trachtman H, Frymoyer A, Lewandowski A, Greenbaum L A, Feig D I, Gipson D S, Warady B A, Goebel J W, Schwartz G J, Lewis K, Anand R, Patel U D
Department of Pediatrics, New York University, New York, New York, USA.
Department of Pediatrics, Stanford University, Palo Alto, California, USA.
Clin Pharmacol Ther. 2015 Jul;98(1):25-33. doi: 10.1002/cpt.127. Epub 2015 May 2.
Hypertension in pediatric kidney transplant recipients contributes to long-term graft loss, yet treatment options--including angiotensin-converting enzyme inhibitors--are poorly characterized in this vulnerable population. We conducted a multicenter, open-label pharmacokinetic (PK) study of daily oral lisinopril in 22 children (ages 7-17 years) with stable kidney transplant function. Standard noncompartmental PK analyses were performed at steady state. Effects on blood pressure were examined in lisinopril-naïve patients (n = 13). Oral clearance declined in proportion to underlying kidney function; however, in patients with low estimated glomerular filtration rate (30-59 ml/min per 1.73m(2)), exposure (standardized to 0.1 mg/kg/day dose) was within the range reported previously in children without a kidney transplant. In lisinopril-naïve patients, 85% and 77% had a ≥ 6 mmHg reduction in systolic and diastolic blood pressure, respectively. Lisinopril was well tolerated. Our study provides initial insight on lisinopril use in children with a kidney transplant, including starting dose considerations.
小儿肾移植受者的高血压会导致长期移植物丢失，然而，在这一脆弱人群中，包括血管紧张素转换酶抑制剂在内的治疗方案的特征尚不明确。我们对22名肾移植功能稳定的儿童（7至17岁）进行了一项多中心、开放标签的赖诺普利每日口服药代动力学（PK）研究。在稳态下进行了标准的非房室PK分析。对未使用过赖诺普利的患者（n = 13）的血压影响进行了检查。口服清除率与基础肾功能成比例下降；然而，在估计肾小球滤过率较低（30 - 59 ml/min per 1.73m²）的患者中，暴露量（标准化为0.1 mg/kg/天剂量）在先前报道的无肾移植儿童的范围内。在未使用过赖诺普利的患者中，分别有85%和77%的患者收缩压和舒张压降低≥6 mmHg。赖诺普利耐受性良好。我们的研究为肾移植儿童使用赖诺普利提供了初步见解，包括起始剂量的考虑因素。
