Rengelshausen Jens, Beedgen Bernd, Tsamouranis Konstantina, Mikus Gerd, Walter-Sack Ingeborg, Haefeli Walter E, Linderkamp Otwin
Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
Eur J Clin Pharmacol. 2006 Sep;62(9):773-7. doi: 10.1007/s00228-006-0153-8. Epub 2006 Jul 25.
Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA).
In an open prospective study, 20 neonates with GA between 22.9 and 32.0 weeks and suspected postnatal bacterial infection received an intravenous loading dose of 5 mg/kg netilmicin over 1 h during the first postnatal day. Netilmicin serum concentrations were determined by an enzyme multiplied immunoassay.
The systemic clearance of netilmicin normalized to body weight (BW) was not significantly different in three GA subgroups (0.59+/- 0.02 ml/min/kg for GA <24 weeks, 0.72+/-0.14 ml/min/kg for GA 24-27 weeks, and 0.62+/-0.19 ml/min/kg for GA 27-32 weeks, P=0.123). Similar results were also obtained for serum elimination half-time and for the distribution volume normalized to BW. Multiple regression analysis showed that systemic clearance and volume of distribution (both not normalized to BW) significantly correlated with BW (P<0.0001) but not with GA. In the entire group, 20% of peak concentrations were below the target of 6 mg/l, and 63% of trough concentrations were above the target of 2 mg/l.
In neonates with very low GA, the pharmacokinetic parameters of netilmicin determined after an intravenous loading dose were not dependent on GA when normalized to BW. A number of neonates did not reach targeted peak and trough netilmicin serum concentrations, suggesting that a higher loading dose and a prolonged dosing interval might enhance the effectiveness and safety of netilmicin in preterm neonates immediately after birth.
药代动力学参数对氨基糖苷类药物的剂量调整很重要，但在新生儿中其变异性很大。本研究在胎龄（GA）极低的早产新生儿出生后第一天，对奈替米星负荷剂量的药代动力学进行了研究。
在一项开放性前瞻性研究中，20例GA在22.9至32.0周之间且怀疑有产后细菌感染的新生儿，在出生后第一天1小时内静脉注射5mg/kg奈替米星负荷剂量。通过酶联免疫分析法测定奈替米星血清浓度。
奈替米星按体重（BW）标准化后的全身清除率在三个GA亚组中无显著差异（GA<24周为0.59±0.02ml/min/kg，GA 24 - 27周为0.72±0.14ml/min/kg，GA 27 - 32周为0.62±0.19ml/min/kg，P = 0.123）。血清消除半衰期和按BW标准化后的分布容积也得到了类似结果。多元回归分析表明，全身清除率和分布容积（均未按BW标准化）与BW显著相关（P<0.0001），但与GA无关。在整个组中，20%的峰浓度低于6mg/l的目标值，63%的谷浓度高于2mg/l的目标值。
在GA极低的新生儿中，静脉注射负荷剂量后测定的奈替米星药代动力学参数按BW标准化后不依赖于GA。一些新生儿未达到奈替米星血清峰浓度和谷浓度目标值，这表明较高的负荷剂量和延长给药间隔可能会提高奈替米星在早产新生儿出生后立即使用时的有效性和安全性。
