Williams B S, Ransom J L, Gal P, Carlos R Q, Smith M, Schall S A
School of Pharmacy, University of North Carolina at Chapel Hill, USA.
Crit Care Med. 1997 Feb;25(2):273-5. doi: 10.1097/00003246-199702000-00013.
To determine the effect of patent ductus arteriosus on the pharmacokinetics of gentamicin in neonates and to examine whether any particular pharmacokinetic parameter is of value as a marker of patent ductus arteriosus.
Cohort study of neonates treated with gentamicin, according to a standard dosing protocol.
A 24-bed, Level III, neonatal intensive care unit.
Neonates treated with gentamicin at the time of admission to the neonatal intensive care unit, using a standard protocol, and who were < 36 wks of gestational age.
All patients received a gentamicin loading dose, and had gentamicin concentrations measured at 2 and 12 hrs after this dose, in order to determine pharmacokinetic parameters and calculate the optimum maintenance dose. Those neonates subsequently diagnosed to have patent ductus arteriosus, based on clinical suspicion and echocardiographic confirmation, were compared with those neonates without clinically suspected patent ductus arteriosus. Gentamicin pharmacokinetic parameters were calculated using a one-compartment model.
A total of 322 courses of gentamicin were administered (patent ductus arteriosus, n = 106; control, n = 216). Gentamicin clearance was decreased in the patent ductus arteriosus group vs. the control group (40.02 vs. 44.73 mL/kg/hr; p < .0108). Volume of distribution was greater for patent ductus arteriosus patients (0.61 L/kg) than for controls (0.54 L/kg) (p < .0002). Also, volume of distribution was a useful marker for presence of patent ductus arteriosus, with a 92% specificity for patent ductus arteriosus.
Gentamicin dosing should be altered in neonates with patent ductus arteriosus to reflect the impact of higher volume of distribution and lower clearance. When the gentamicin volume of distribution exceeds 0.7 L/kg, it may be of predictive value for the presence of patent ductus arteriosus.
确定动脉导管未闭对新生儿庆大霉素药代动力学的影响，并检查是否有任何特定的药代动力学参数可作为动脉导管未闭的标志物。
按照标准给药方案对接受庆大霉素治疗的新生儿进行队列研究。
一家拥有24张床位的三级新生儿重症监护病房。
新生儿重症监护病房收治的、使用标准方案治疗且胎龄小于36周的新生儿，这些新生儿在入院时接受了庆大霉素治疗。
所有患者均接受庆大霉素负荷剂量，并在给药后2小时和12小时测量庆大霉素浓度，以确定药代动力学参数并计算最佳维持剂量。随后，根据临床怀疑和超声心动图确认诊断为动脉导管未闭的新生儿与无临床疑似动脉导管未闭的新生儿进行比较。庆大霉素药代动力学参数采用一室模型计算。
共给予322个疗程的庆大霉素（动脉导管未闭组，n = 106；对照组，n = 216）。与对照组相比，动脉导管未闭组的庆大霉素清除率降低（40.02 vs. 44.73 mL/kg/hr；p <.0108）。动脉导管未闭患者的分布容积（0.61 L/kg）大于对照组（0.54 L/kg）（p <.0002）。此外，分布容积是动脉导管未闭存在的有用标志物，对动脉导管未闭的特异性为92%。
动脉导管未闭的新生儿应调整庆大霉素剂量，以反映分布容积增加和清除率降低的影响。当庆大霉素分布容积超过0.7 L/kg时，可能对动脉导管未闭的存在具有预测价值。
