Bethell D B, Day N P, Dung N M, McMullin C, Loan H T, Tam D T, Minh L T, Linh N T, Dung N Q, Vinh H, MacGowan A P, White L O, White N J
Centre for Tropical Diseases, Ho Chi Minh City, Vietnam.
Antimicrob Agents Chemother. 1996 Sep;40(9):2167-72. doi: 10.1128/AAC.40.9.2167.
The pharmacokinetics of oral and intravenous ofloxacin (7.5 mg.kg of body weight-1 given over 30 min) were studied in an open crossover study of 17 Vietnamese children, aged between 5 and 14 years, with acute uncomplicated typhoid fever. Following oral administration, the median (95% confidence interval [CI]) time to peak concentration of ofloxacin in serum (Cmax) was 1.7 h (1.4 to 1.9 h) and the mean (95% CI) Cmax was 5.5 mg.liter-1 (4.7 to 6.3 mg.liter-1) compared with a Cmax of 8.7 mg.liter-1 (7.6 to 9.7 mg.liter-1) following the intravenous infusion. The median (95% CI) total apparent volume of distribution following the first intravenous dose, 1.35 liter.kg-1 (1.17 to 1.73 liter.kg-1), was significantly larger than that following the second dose, 0.99 liter.kg-1 (0.86 to 1.17 liter.kg-1; P < 0.0005), although the estimates for systemic clearance were similar: 0.255 liter.kg-1 h-1 (0.147 to 0.325 liter.kg-1 h-1) compared with 0.172 liter.kg-1 h-1 (0.127 to 0.292 liter.kg-1 h-1; P = 0.14). The mean residence times (95% CI) following intravenous and oral administration were similar: 5.24 h (4.84 to 6.58 h) and 6.24 h (5.32 to 7.85 h), respectively. The mean (95% CI) oral bioavailability was 91% (74 to 109%). The peak concentrations in serum were 10 to 100 times higher than the maximum MICs for ofloxacin against multidrug-resistant Salmonella typhi isolated in this area. Although the systemic clearance values were higher than those reported previously for adults, these data overall suggest that weight-or area-adjusted dose regimens for the treatment of typhoid in older children should be the same as those for adults.
在一项针对17名年龄在5至14岁、患有急性非复杂性伤寒热的越南儿童的开放性交叉研究中，对口服和静脉注射氧氟沙星（按体重7.5mg·kg⁻¹，30分钟内给药）的药代动力学进行了研究。口服给药后，血清中氧氟沙星达到峰值浓度（Cmax）的中位时间（95%置信区间[CI]）为1.7小时（1.4至1.9小时），平均（95%CI）Cmax为5.5mg·L⁻¹（4.7至6.3mg·L⁻¹），而静脉输注后的Cmax为8.7mg·L⁻¹（7.6至9.7mg·L⁻¹）。首次静脉给药后的中位（95%CI）总表观分布容积为1.35L·kg⁻¹（1.17至1.73L·kg⁻¹），显著大于第二次给药后的0.99L·kg⁻¹（0.86至1.17L·kg⁻¹；P<0.0005），尽管全身清除率的估计值相似：分别为0.255L·kg⁻¹·h⁻¹（0.147至0.325L·kg⁻¹·h⁻¹）和0.172L·kg⁻¹·h⁻¹（0.127至0.292L·kg⁻¹·h⁻¹；P = 0.14）。静脉注射和口服给药后的平均驻留时间（95%CI）相似：分别为5.24小时（4.84至6.58小时）和6.24小时（5.32至7.85小时）。平均（95%CI）口服生物利用度为91%（74至109%）。血清中的峰值浓度比该地区分离出的耐多药伤寒沙门菌对氧氟沙星的最大MIC高10至100倍。尽管全身清除率值高于先前报道的成人值，但这些数据总体表明，大龄儿童伤寒治疗的体重或体表面积调整剂量方案应与成人相同。
