Pharmacokinetics of oral and intravenous ofloxacin in children with multidrug-resistant typhoid fever

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 (C-max) was 1.7 h (1.1 to 1.9 h) and the mean (95% CI) C-max was 5.5 mg . liter(-1) (4.7 to 6.3 mg . liter(-1)) compared with a C-max 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) (0.117 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 he the same as those for adults.