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

Abstract

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 (1.4 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 (0.147 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.