Sánchez-Alcaraz A, Vargas A, Quintana M B, Rocher A, Querol J M, Poveda J L, Hermenegildo M
Department of Pharmacy, Arnau de Vilanova Hospital, Valencia, Spain.
J Clin Pharm Ther. 1998 Oct;23(5):367-73. doi: 10.1046/j.1365-2710.1998.00174.x.
To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity.
Patients undergoing treatment with i.v. tobramycin (4 mg/kg/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment.
The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g/ml in the two groups (100%). Peak concentrations were > 6 microg/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+/-2.89 microg/ml in OD vs. 6.53+/-1.45 microg/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+/-0.03/h in OD vs. 0.24+/-0.06/h in TD), t1/2, (4.95+/-1.41 h in OD vs. 3.07+/-0.71 h in TD), Vd (0.35+/-0.11 l/kg in OD vs. 0.33+/-0.09 l/kg in TD), Cl (0.86+/-0.29 ml/min/kg in OD vs. 1.28+/-0.33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function.
This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.
评估妥布霉素的给药方案（每日一次与每日两次）对稳态血清浓度及毒性的影响。
接受静脉注射妥布霉素（4毫克/千克/天）治疗的患者被随机分为两组。OD组（n = 22）接受每日一次的妥布霉素剂量，TD组（n = 21）接受相同剂量，分两次每日给药。通过酶联免疫分析法测定妥布霉素血清浓度（峰值和谷值）。在治疗前、治疗期间及治疗结束后立即监测患者的肾功能和听力功能。
两组在性别、年龄、体重和肾功能方面具有可比性。在平均每日剂量、治疗持续时间或累积剂量方面未发现统计学显著差异。两组的谷浓度均<2微克/毫升（100%）。OD组100%的患者峰值浓度>6微克/毫升，TD组为67%（P<0.01）。平均峰值浓度有显著差异：OD组为11.00±2.89微克/毫升，TD组为6.53±1.45微克/毫升（P<0.01）。药代动力学参数为：Ke，OD组为0.15±0.03/小时，TD组为0.24±0.06/小时；t1/2，OD组为4.95±1.41小时，TD组为3.07±0.71小时；Vd，OD组为0.35±0.11升/千克，TD组为0.33±0.09升/千克；Cl，OD组为0.86±0.29毫升/分钟/千克，TD组为1.28±0.33毫升/分钟/千克。OD组73%的患者血清肌酐升高，TD组为57%，但均无肾毒性证据。在TD组，3名患者出现听力功能下降，其中1名患者听力损失-30分贝，而在OD组只有1名患者出现听力功能下降。
这项小型研究表明，妥布霉素每日一次给药方案至少与每日两次给药方案同样有效，且毒性不更高，甚至可能更低。采用单剂量疗法时，无需测定峰值浓度，仅需监测谷值样本以确保浓度低于2微克/毫升。
