Balis F M, Pizzo P A, Butler K M, Hawkins M E, Brouwers P, Husson R N, Jacobsen F, Blaney S M, Gress J, Jarosinski P
Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Infect Dis. 1992 Jan;165(1):99-104. doi: 10.1093/infdis/165.1.99.
The pharmacokinetics of intravenous and oral 2',3'-dideoxyinosine (ddI) and the relationships between pharmacokinetic parameters and measures of response were studied in 48 human immunodeficiency virus-infected children. Disappearance of ddI from plasma after the intravenous dose was rapid and biexponential, with half-lives of 12 min and 1.0 h and a total clearance of 510 +/- 180 ml/min/m2. After oral administration, ddI absorption was limited and variable (mean bioavailability, 19% +/- 17%). A plasma ddI concentration-response relationship was observed for both decline in viral p24 antigen levels and improvement in intelligence quotient score. A limited sampling model was developed that accurately predicts the area under the ddI plasma concentration-time curve from one to three plasma samples. Although this pharmacokinetic study was done in children, the results also have relevance to adults and suggest that individualization of dose and schedule through therapeutic drug monitoring may be necessary to achieve optimal response.
在48名感染人类免疫缺陷病毒的儿童中研究了静脉注射和口服2',3'-双脱氧肌苷（ddI）的药代动力学以及药代动力学参数与反应指标之间的关系。静脉给药后，ddI从血浆中的消失迅速且呈双指数，半衰期分别为12分钟和1.0小时，总清除率为510±180毫升/分钟/平方米。口服给药后，ddI的吸收有限且变化不定（平均生物利用度为19%±17%）。对于病毒p24抗原水平的下降和智商得分的提高，均观察到血浆ddI浓度与反应的关系。开发了一种有限采样模型，该模型可根据一至三个血浆样本准确预测ddI血浆浓度-时间曲线下的面积。尽管这项药代动力学研究是在儿童中进行的，但结果对成人也有相关性，并表明通过治疗药物监测实现剂量和给药方案的个体化可能是实现最佳反应所必需的。
