文章基本信息

标题：A Predictive Model for Area Under the Concentration versus Time Curve of Cyclosporin A Using Several Routine Monitoring Results in Renal Transplant Patients
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作者：Nobuhito SHIBATA ; Taro HAYAKAWA ; Nobuo HOSHINO 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1997
卷号：20
期号：8
页码：897-903
DOI：10.1248/bpb.20.897
出版社：The Pharmaceutical Society of Japan
摘要：We created a predictive model for the area under the concentration versus time curve (AUC) of cyclosporin A (CsA) using routine monitoring results, and examined its clinical utility. Based on 48 clinical time courses accumulated from renal transplant patients, the AUC predictive model was created. An estimate of the AUC_0-8 (integrated from time zero to 8 h) was then given as follows : AUC_0-8=5673.1×log(TL)+9342.8×log(OB)+64.1×D_prd×869.4×DTK-168.9×HCT-161.2×SCr-11.3×GPT+3.0×PL-588.6×SEX-24794.5. In this model, the AUC_0-8(ng·h/ml) is given as a function of the CsA trough levels (TL, ng/ml), obesity (OB, %), daily dose of prednisolone (D_prd, mg/d), donor type of kidney (DTK), hematocrit (HCT, %), serum creatinine (SCr, mg/dl), glutamate-pyruvate transaminase activity (GPT, IU/l), plasma lipids (PL, mg/dl) and sex distinction (SEX). The Statistical significance of this multiple regression was p_<0.00001 (R²=0.862, n=48), and the day after transplantation, neither the administered oral dose of CsA, or the patient's age had any contribution to the regression. The predictive performance of this model was almost equal to that of the existing method which used 3-point data on the concentration versus time curve. In clinical adaptation for renal transplant patients, the steady-state concentration of CsA (C_ss) based on the AUC_0-8 predictive model was significantly decreased during acute gastroenteritis or before acute rejection, whereas nephrotoxicity was increased, even though CsA trough levels were within a normal therapeutic range (100-200 ng/ml). These findings suggest that the created AUC_0-8 predictive model using routine monitoring results, i.e., the trough level of CsA, biochemical tests, a daily dose of predorinsolone (PRD), and basic patient information, is convenient as a monitoring device for CsA therapy, and is satisfactory in clinical practice.
关键词：cyclosporin A;predictive model;AUC monitoring;trough level monitoring;disease state;renal transplantation