Reed M D, Yamashita T S, Knupp C K, Veazey J M, Blumer J L
Center for Drug Research, Rainbow Babies and Childrens Hospital, Department of Pediatrics, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Antimicrob Agents Chemother. 1997 Aug;41(8):1783-7. doi: 10.1128/AAC.41.8.1783.
The pharmacokinetic characteristics of cefepime were determined after first dose (n = 35) and again under steady-state conditions (n = 31) with a group of 37 infants and children. In eight subjects, a cefepime dose given by intramuscular injection was substituted for an intravenous dose, and disposition characteristics were studied again. Study subjects ranged in age from 2.1 months to 16.4 years, and all had normal renal function. Each patient received 50 mg of cefepime/kg of body weight intravenously every 8 h, up to a total maximum individual dose of 2 g. With the exception of one study patient who received a single cefepime dose for surgical prophylaxis, the patients received cefepime for 2 to 13 days. Elimination half-life (t1/2), steady-state volume of distribution, total body clearance, and renal clearance after first dose administration averaged 1.7 h, 0.35 liter/kg, and 3.1 and 1.9 ml/min/kg, respectively. Although cefepime t1/2 and mean residence time (MRT) were slightly longer for subjects <6 months of age than for older subjects, no differences in cefepime disposition characteristics between first dose and steady-state evaluations were observed. t1/2 (1.8 versus 1.9 h) and MRT (2.3 versus 3.2 h) were slightly prolonged after intramuscular administration, reflecting the influence of absorption from the intramuscular injection site on cefepime elimination. Bioavailability after intramuscular administration averaged 82% (range, 61 to 124%). Fifty-seven percent of the first dose and 88.9% of the last dose were recovered as unchanged drug in urine over the 8- and 24-h sampling periods, respectively. These pharmacokinetic data support a single cefepime dosing strategy for patients > or =2 months of age. The integration of the cefepime pharmacokinetic data generated in our study with the MICs for important pathogens responsible for infections in infants and children supports the administration of a dose of 50 mg of cefepime/kg every 12 h for patients > or =2 months of age to treat infections caused by pathogens for which cefepime MICs are < or =8 mg/liter.
在一组37名婴幼儿和儿童中，首次给药后（n = 35）以及稳态条件下再次给药时（n = 31）测定了头孢吡肟的药代动力学特征。在8名受试者中，用肌肉注射的头孢吡肟剂量替代静脉注射剂量，并再次研究其处置特征。研究对象年龄范围为2.1个月至16.4岁，且肾功能均正常。每位患者每8小时静脉注射50mg/kg体重的头孢吡肟，最大个体总剂量可达2g。除一名接受单次头孢吡肟剂量用于手术预防的研究患者外，其余患者接受头孢吡肟治疗2至13天。首次给药后的消除半衰期（t1/2）、稳态分布容积、总体清除率和肾清除率平均分别为1.7小时、0.35升/千克、3.1和1.9毫升/分钟/千克。虽然6个月龄以下受试者的头孢吡肟t1/2和平均驻留时间（MRT）比大龄受试者略长，但首次给药和稳态评估之间头孢吡肟处置特征未观察到差异。肌肉注射后t1/2（1.8对1.9小时）和MRT（2.3对3.2小时）略有延长，反映了肌肉注射部位吸收对头孢吡肟消除的影响。肌肉注射后的生物利用度平均为82%（范围为61%至124%）。在8小时和24小时采样期内，首次给药剂量的57%和末次给药剂量的88.9%分别以原形药物形式在尿液中回收。这些药代动力学数据支持2月龄及以上患者采用单次头孢吡肟给药策略。我们研究中产生的头孢吡肟药代动力学数据与婴幼儿感染重要病原体的最低抑菌浓度（MIC）相结合，支持2月龄及以上患者每12小时给予50mg/kg头孢吡肟剂量，以治疗由头孢吡肟MIC≤8mg/L的病原体引起的感染。
