title: 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 (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.
authors.affiliation: Centre for Tropical Diseases, Ho Chi Minh City, Vietnam.
authors.forename: D B
authors.initials: DB
authors.lastname: Bethell
authors.forename: N P
authors.initials: NP
authors.lastname: Day
authors.forename: N M
authors.initials: NM
authors.lastname: Dung
authors.forename: C
authors.initials: C
authors.lastname: McMullin
authors.forename: H T
authors.initials: HT
authors.lastname: Loan
authors.forename: D T
authors.initials: DT
authors.lastname: Tam
authors.forename: L T
authors.initials: LT
authors.lastname: Minh
authors.forename: N T
authors.initials: NT
authors.lastname: Linh
authors.forename: N Q
authors.initials: NQ
authors.lastname: Dung
authors.forename: H
authors.initials: H
authors.lastname: Vinh
authors.forename: A P
authors.initials: AP
authors.lastname: MacGowan
authors.forename: L O
authors.initials: LO
authors.lastname: White
authors.forename: N J
authors.initials: NJ
authors.lastname: White
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D018432:Drug Resistance, Multiple; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012485:Salmonella typhi / Q000187:drug effects; D014435:Typhoid Fever / Q000378:metabolism* / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D015242:Ofloxacin