Siber G R, Echeverria P, Smith A L, Paisley J W, Smith D H
J Infect Dis. 1975 Dec;132(6):637-51. doi: 10.1093/infdis/132.6.637.
Peak concentrations and half-life of gentamicin in serum were measured after 140 intravenous and 13 intramuscular doses in 52 children and 17 adults with normal levels of creatinine in serum. Marked interpatient variation in peak concentrations and half-life of gentamicin was observed, but individual patients tended to have similar values on repeated determinations. Age markedly affected the peak concentrations: a 1-mg/kg dose produced mean peak concentrations of 1.58, 2.03, and 2.81 mug/ml in the one-half to five, five to 10, and greater than 10 year age groups, respectively. This age-related change in dose response was diminished when the dose was calculated on the basis of body surface area. Patients in whom gentamicin had a short half-life, patients with fever, and adults with a high extracellular fluid volume had low peak concentrations. The mean half-life after intravenous administration was 75 min (range, 26-230 min). The mean half-life was 29 min longer after intramuscular dosage (p less than 0.01). A low rate of creatinine clearance was associated with a long half-life; fever and anemia were associated with a short half-life. The dosage of gentamicin necessary to produce mean peak serum concentrations between 4 mug/ml and 6 mug/ml was 60 mg/m2 per dose for all age groups or 2.5 mg/kg per dose for ages one-half to five years, 2.0 mg/kg per dose for ages five to 10 years, and 1.5 mg/kg per dose for ages greater than 10 years.
对52名儿童和17名血清肌酐水平正常的成年人进行了140次静脉注射和13次肌肉注射庆大霉素后,测定了血清中庆大霉素的峰值浓度和半衰期。观察到庆大霉素的峰值浓度和半衰期在患者之间存在显著差异,但个体患者在重复测定时往往具有相似的值。年龄对峰值浓度有显著影响:1mg/kg剂量在1.5至5岁、5至10岁和大于10岁年龄组中产生的平均峰值浓度分别为1.58、2.03和2.81μg/ml。当根据体表面积计算剂量时,这种与年龄相关的剂量反应变化会减小。庆大霉素半衰期短的患者、发热患者以及细胞外液量高的成年人峰值浓度较低。静脉给药后的平均半衰期为75分钟(范围为26至230分钟)。肌肉注射后的平均半衰期长29分钟(p<0.01)。肌酐清除率低与半衰期长有关;发热和贫血与半衰期短有关。所有年龄组产生4μg/ml至6μg/ml平均血清峰值浓度所需的庆大霉素剂量为每剂量60mg/m²,1.5至5岁年龄组为每剂量2.5mg/kg,5至10岁年龄组为每剂量2.0mg/kg,大于10岁年龄组为每剂量1.5mg/kg。