Long D, Koren G, James A
Division of Clinical Pharmacology, Hospital for Sick Children, Toronto, Ontario, Canada.
J Pediatr. 1987 Dec;111(6 Pt 1):918-21. doi: 10.1016/s0022-3476(87)80219-6.
Our study aimed to determine the least number of samples that are required to obtain accurate pharmacokinetic parameters in neonates. Patients treated with either netilmicin or ceftazidime had between five and eight samples drawn for drug concentration measurement after the first or the last dose of the drug. Pharmacokinetic parameters were calculated using all the available points as a reference and then recalculated with 2, 3, or 4 points. Systemic clearance and volume of distribution were significantly different from the reference value when 2 points were used for netilmicin after the first dose and ceftazidime after the last dose. Had parameters obtained from 2 points been used, mean dosage would have been underestimated by 15% for ceftazidime and 11% for netilmicin, and some patients would have received only 65% of the dose calculated from all available points. When 3 points were used, dosage would have been underestimated by a mean of only 1% for ceftazidime and 5% for netilmicin when compared with the dosage estimated from the reference parameters. We conclude that 3 concentration time points may be all that are required for estimation of pharmacokinetic parameters sufficiently accurate for practical purposes in neonates.
我们的研究旨在确定获得新生儿准确药代动力学参数所需的最少样本数量。接受奈替米星或头孢他啶治疗的患者在首次或末次给药后采集了5至8份样本用于药物浓度测量。药代动力学参数以所有可用数据点为参考进行计算，然后用2、3或4个数据点重新计算。当首次给药后奈替米星和末次给药后头孢他啶使用2个数据点时，全身清除率和分布容积与参考值有显著差异。若使用从2个数据点获得的参数，头孢他啶的平均剂量会被低估15%，奈替米星会被低估11%，并且一些患者将仅接受从所有可用数据点计算出的剂量的65%。与根据参考参数估算的剂量相比，当使用3个数据点时，头孢他啶的剂量平均仅被低估1%，奈替米星被低估5%。我们得出结论，对于新生儿实际应用而言，3个浓度时间点可能足以估算出足够准确的药代动力学参数。
