Nahata M C, Powell D A, Durrell D E, Miller M A
Br J Clin Pharmacol. 1986 Mar;21(3):325-7. doi: 10.1111/j.1365-2125.1986.tb05198.x.
Tobramycin is commonly used at a dose of 2.5 mg kg-1 12h-1, but this regimen often results in trough serum concentrations exceeding 2 mg l-1. Because of limited data in infants weighing less than 1,000 g at birth, we studied eight newborn infants (gestational age 24-30 weeks; postnatal age 3 X 4 days; birth weight 0.60-0.97 kg) at a modified dosing regimen of 2.5 mg kg-1 18 h-1 or 3.0 mg kg-1 24 h-1. Tobramycin peak and trough serum concentrations ranged from 6.0-10.8 (7.8 +/- 1.5) mg l-1 and 1.2-2.4 (1.7 +/- 0.4) mg l-1, respectively. Serum concentration exceeded 2 mg l-1 in seven of eight patients at 12 h and two of eight at 18 h; none had a trough serum concentration above 2 mg l-1 at 24 h. Total body clearance ranged from 0.55 to 0.82 (0.69 +/- 0.10) ml min-1 kg-1; apparent volume of distribution ranged from 0.44 to 0.71 (0.59 +/- 0.10) 1 kg-1; and elimination half-life ranged from 7.7 to 12.6 (9.9 +/- 1.5) h. These data indicate that the modified dosage regimen of 2.5 mg kg-1 18 h-1 or 3.0 mg kg-1 24 h-1 appears to be more acceptable than the current regimen in achieving effective and safe peak and trough serum concentration of tobramycin in newborn infants weighing less than 1 kg at birth.
妥布霉素常用剂量为2.5毫克/千克，每12小时一次，但这种给药方案常常导致血清谷浓度超过2毫克/升。由于出生体重不足1000克的婴儿的数据有限，我们研究了8例新生儿（胎龄24 - 30周；出生后3 - 4天；出生体重0.60 - 0.97千克），采用2.5毫克/千克，每18小时一次或3.0毫克/千克，每24小时一次的改良给药方案。妥布霉素血清峰浓度和谷浓度分别为6.0 - 10.8（7.8±1.5）毫克/升和1.2 - 2.4（1.7±0.4）毫克/升。8例患者中有7例在12小时时血清浓度超过2毫克/升，8例中有2例在18小时时超过；24小时时无1例血清谷浓度高于2毫克/升。总体清除率为0.55至0.82（0.69±0.10）毫升/分钟/千克；表观分布容积为0.44至0.71（0.59±0.10）升/千克；消除半衰期为7.7至12.6（9.9±1.5）小时。这些数据表明，对于出生体重不足1千克的新生儿，2.5毫克/千克，每18小时一次或3.0毫克/千克，每24小时一次的改良给药方案在实现妥布霉素有效且安全的血清峰浓度和谷浓度方面似乎比当前方案更可接受。
