Herngren L, Broberger U, Wretlind B
Acta Paediatr Scand. 1986 Mar;75(2):198-204. doi: 10.1111/j.1651-2227.1986.tb10184.x.
In a retrospective study of 72 neonates during treatment with gentamicin, poor correlation was found between dosage based on body weight and gentamicin serum concentrations. Calculation of adequate gentamicin dosage regimen during steady-state based on individual pharmacokinetic parameters according to Gibaldi & Perrier was then studied in 35 newborn infants during therapy. Predictions were based on gentamicin serum concentrations taken prior to and 1, 3, and 5 hours after the first (n = 8) or second (n = 12) dose (group A), or only prior to and one hour after dose (group B, n = 15). Half-life (t1/2), apparent volume of distribution (Vd), body clearance (Clbody) and elimination rate constant (beta) were not significantly different when calculated after the first or second dose or during steady-state. The correlation between predicted and observed gentamicin concentration was high in both groups (p less than 0.005) and the slopes congruent with unity. After dose or interval correction, 73% of the observed predose concentrations (mean 2.0 micrograms/ml) were within 1 microgram/ml of predicted values. One hour after dose the predicted (mean 5.7 micrograms/ml) and observed (mean 6.2 micrograms/ml) values were not significantly different. Higher precision was noted when the predictions were based on 4 samples (group A) compared to 2 (group B). Since the calculations may be performed by a simple desk calculator rapid advice may be given to the clinical staff on adequate gentamicin dosage even in small severely ill preterm infants.
在一项对72例接受庆大霉素治疗的新生儿的回顾性研究中,发现基于体重的剂量与庆大霉素血清浓度之间相关性较差。随后,在35例新生儿治疗期间,根据吉巴尔迪(Gibaldi)和佩里尔(Perrier)的方法,基于个体药代动力学参数研究了稳态时庆大霉素的合适剂量方案。预测基于首次(n = 8)或第二次(n = 12)给药前以及给药后1、3和5小时采集的庆大霉素血清浓度(A组),或仅基于给药前和给药后1小时采集的血清浓度(B组,n = 15)。首次或第二次给药后或稳态期间计算的半衰期(t1/2)、表观分布容积(Vd)、机体清除率(Clbody)和消除速率常数(β)无显著差异。两组中预测的和观察到的庆大霉素浓度之间相关性都很高(p小于0.005),且斜率与1一致。经过剂量或间隔校正后,73%观察到的给药前浓度(平均2.0微克/毫升)与预测值相差在1微克/毫升以内。给药后1小时,预测值(平均5.7微克/毫升)和观察值(平均6.2微克/毫升)无显著差异。与基于2个样本(B组)相比,基于4个样本(A组)进行预测时精度更高。由于计算可通过简单的台式计算器完成,因此即使对于病情严重的早产婴儿,也可迅速为临床工作人员提供关于庆大霉素合适剂量的建议。