Yakatan G J, Smith R B, Leff R D, Kay J L
Clin Pharmacol Ther. 1978 Jul;24(1):90-4. doi: 10.1002/cpt197824190.
Neonates undergoing blood exchange often receive concomitant therapy. Questions may be raised whether dosage regimen alterations are necessary to replace drug lost as a result of the exchange procedure. Our study reports the changes in plasma concentration of kanamycin during an exchange transfusion and a pharmacokinetic analysis of the effect of the exchange on drug elimination. The relationships of the volumes of distribution, elimination rate constant, and time after dosing on the fraction of the dose eliminated in the blood exchange are developed on the basis of a one-compartment body model. Computer simulations using the equations developed were used to estimate the fraction of a dose that might be removed as a result of an exchange transfusion. As the disposition rate constant or the apparent volume of distribution increase, i.e., the clearance of the drug increases, the fraction of the dose removed by the exchange process decreases. Thus, significant amounts of drug removal may occur in an exchange transfusion for drugs with low clearance when the exchange is initiated early in the drug dosing interval. In our study, only 3% of the kanamycin dose was removed as a result of the exchange process, and dosing adjustment would not be required. This was in part due to initiation of the exchange late in the dosing interval, although the maximum calculated percentage of the dose which could have been removed under the exchange conditions employed was only 10%.
接受换血治疗的新生儿通常会同时接受其他治疗。对于是否需要调整给药方案以补充因换血过程而损失的药物，可能会存在疑问。我们的研究报告了换血输血期间卡那霉素血浆浓度的变化以及换血对药物消除影响的药代动力学分析。基于单室模型，建立了分布容积、消除速率常数和给药后时间与换血中消除剂量分数之间的关系。使用所建立的方程进行计算机模拟，以估计因换血输血可能去除的剂量分数。随着处置速率常数或表观分布容积增加，即药物清除率增加，换血过程去除的剂量分数降低。因此，对于清除率低的药物，如果在给药间隔早期开始换血，则换血输血中可能会发生大量药物清除。在我们的研究中，换血过程仅去除了3%的卡那霉素剂量，因此无需调整给药剂量。部分原因是在给药间隔后期开始换血，尽管在所采用的换血条件下计算出的可能去除的最大剂量百分比仅为10%。
