Pharmacokinetics of oral and intravenous ofloxacin in children with multidrug-resistant typhoid fever.
Bethell DB., Day NP., Dung NM., McMullin C., Loan HT., Tam DT., Minh LT., Linh NT., Dung NQ., Vinh H., MacGowan AP., White LO., White NJ.
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.