吲哚美辛在新生儿中的药代动力学：分布容积作为动脉导管未闭永久性闭合标志物的价值。

Indomethacin pharmacokinetics in neonates: the value of volume of distribution as a marker of permanent patent ductus arteriosus closure.

作者信息

Gal P, Ransom J L, Weaver R L, Schall S, Wyble L E, Carlos R Q, Brown Y

机构信息

Greensboro Area Health Education Center, Moses H. Cone Memorial Hospital, NC 27401.

出版信息

Ther Drug Monit. 1991 Jan;13(1):42-5.

PMID:2057990

Abstract

Indomethacin (INDO) pharmacokinetics were examined in 18 neonates on 19 occasions, before and after patent ductus arteriosus (PDA) closure. Patients received INDO as an initial dose of 0.25 mg/kg intravenously, and INDO serum concentrations were measured 2 and 8 h after the dose. Subsequent doses were individualized based on clinical response, toxicity, and INDO pharmacokinetics. PDA status was confirmed echocardiographically at the start and end of therapy. INDO pharmacokinetic parameters varied from dose-to-dose within the same patient, and wide interpatient variability was also observed. Pre- and post-PDA closure, only INDO volume of distribution differed significantly (p less than 0.001) with mean values of 0.36 (+/- 0.06) L/kg and 0.26 (+/- 0.08) L/kg. The reason for this occurrence remains unclear. However, a new application for pharmacokinetics as a probe of physiology is demonstrated.

摘要

在18例新生儿的19次检查中，在动脉导管未闭（PDA）闭合前后检测了吲哚美辛（INDO）的药代动力学。患者静脉注射初始剂量为0.25mg/kg的INDO，并在给药后2小时和8小时测量INDO血清浓度。后续剂量根据临床反应、毒性和INDO药代动力学进行个体化调整。在治疗开始和结束时通过超声心动图确认PDA状态。同一患者不同剂量之间的INDO药代动力学参数有所不同，并且患者间也存在很大的变异性。PDA闭合前后，仅INDO分布容积有显著差异（p小于0.001），平均值分别为0.36（±0.06）L/kg和0.26（±0.08）L/kg。这种现象的原因尚不清楚。然而，展示了药代动力学作为生理学探针的一种新应用。