van den Anker J N, Schoemaker R C, Hop W C, van der Heijden B J, Weber A, Sauer P J, Neijens H J, de Groot R
Department of Pediatrics and Epidemiology, Erasmus University, Rotterdam, The Netherlands.
Clin Pharmacol Ther. 1995 Dec;58(6):650-9. doi: 10.1016/0009-9236(95)90021-7.
The objectives of this study were (1) to determine the effects of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtration rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life.
Multiple-dose pharmacokinetics of ceftazidime (administered twice daily in a 25 or 50 mg/kg body weight intravenous dose) were evaluated in 136 preterm infants on day 3 of life. Blood samples were collected from an arterial catheter 0, 1/2, 1, 2, 4, 8, and 12 hours after the intravenous dose. An HPLC method was used to determine ceftazidime concentrations in serum. The GFR was studied simultaneously by means of the 24-hour continuous inulin infusion technique.
The total body clearance, volume of distribution, and elimination serum half-life of ceftazidime (mean +/- SD) were 55.7 +/- 34.4 ml/hr (37.3 +/- 11.9 ml/hr/kg), 496 +/- 228 ml (350 +/- 96 ml/kg), and 6.95 +/- 2.32 hours, respectively. The mean +/- SD peak and trough levels were 114.9 +/- 39.4 and 33.9 +/- 17.8 mg/L. All infants had a serum trough level above 5 mg/L. Clearance and volume of distribution of ceftazidime and GFR increased significantly with increasing gestational age, whereas serum trough levels and serum half-life of ceftazidime decreased significantly with increasing gestational age. Ceftazidime clearance increased significantly with increasing GFR. Prenatal exposure to indomethacin resulted in significantly lower GFR values and ceftazidime clearances.
Dosage recommendations for ceftazidime administration in preterm infants during the first week of life should be based on gestational age and GFR. Additional adjustments in dosage are indicated in preterm infants who are exposed prenatally to indomethacin.
本研究的目的是：（1）确定胎龄对早产儿头孢他啶药代动力学的影响；（2）将这些影响与肾小球滤过率（GFR）的变化相关联；（3）为出生第3天的早产儿制定合适的剂量建议。
对136例出生第3天的早产儿进行了头孢他啶多剂量药代动力学研究（以25或50mg/kg体重的静脉剂量每日给药两次）。静脉给药后0、1/2、1、2、4、8和12小时从动脉导管采集血样。采用高效液相色谱法测定血清中头孢他啶浓度。同时采用24小时持续输注菊粉技术研究GFR。
头孢他啶的总体清除率、分布容积和血清消除半衰期（均值±标准差）分别为55.7±34.4ml/小时（37.3±11.9ml/小时/千克）、496±228ml（350±96ml/千克）和6.95±2.32小时。平均±标准差的峰浓度和谷浓度分别为114.9±39.4和33.9±17.8mg/L。所有婴儿的血清谷浓度均高于5mg/L。头孢他啶的清除率和分布容积以及GFR随胎龄增加而显著增加，而头孢他啶的血清谷浓度和血清半衰期随胎龄增加而显著降低。头孢他啶清除率随GFR增加而显著增加。产前暴露于吲哚美辛导致GFR值和头孢他啶清除率显著降低。
出生后第一周早产儿头孢他啶给药的剂量建议应基于胎龄和GFR。产前暴露于吲哚美辛的早产儿需要进一步调整剂量。
