Medeiros Mara, Pérez-Urizar José, Mejía-Gaviria Natalia, Ramírez-López Eduardo, Castañeda-Hernández Gilberto, Muñoz Ricardo
Departamento de Nefrología, Hospital Infantil de México Federico Gómez, Dr. Márquez 162 Colonia Doctores, México D.F., CP 06720, Mexico.
Pediatr Nephrol. 2007 Jan;22(1):84-90. doi: 10.1007/s00467-006-0300-6. Epub 2006 Oct 20.
In this paper, we report the pharmacokinetics changes observed in seven children with steroid-resistant nephrotic syndrome (SRNS). They received cyclosporine A (CsA) microemulsion 6 mg/kg/day and, one week later, they were admitted to perform a 12-h pharmacokinetic profile with eight time sample points. The pharmacokinetic profile was repeated at 24 weeks of treatment, when all patients achieved remission. Blood concentration against time curves were constructed for each patient at weeks 1 and 24 of CsA treatment. Peak concentrations (C (max)) and the time needed to reach peak concentrations (t (max)) were directly determined from these plots. The area under the curve (AUC) was estimated by the trapezoidal rule. There was a statistically significant difference of the AUC, trough levels, and t (max) between weeks 1 and 24, with a decrease of AUC from 5,211 ngh/ml in week 1 to 3,289 ngh/ml in week 24, the trough levels decreased from 157 ng/ml to 96 ng/ml, and the t (max) decreased from 1.85 h to 1.00 h. The higher CsA bioavailability during the nephrotic state has to be considered when managing patients, since the target AUC cannot be the same throughout the treatment.
在本文中,我们报告了在7名类固醇抵抗型肾病综合征(SRNS)儿童中观察到的药代动力学变化。他们接受了每天6mg/kg的环孢素A(CsA)微乳剂治疗,一周后入院进行12小时药代动力学分析,设置8个时间采样点。在治疗24周时重复进行药代动力学分析,此时所有患者均达到缓解状态。针对每位患者,在CsA治疗的第1周和第24周绘制血药浓度-时间曲线。峰浓度(C(max))和达到峰浓度所需时间(t(max))直接从这些图中确定。曲线下面积(AUC)通过梯形法则估算。第1周和第24周之间的AUC、谷浓度和t(max)存在统计学显著差异,AUC从第1周的5211ngh/ml降至第24周的3289ngh/ml,谷浓度从157ng/ml降至96ng/ml,t(max)从1.85小时降至1.00小时。在治疗患者时,必须考虑肾病状态下CsA较高的生物利用度,因为在整个治疗过程中目标AUC不可能相同。