title: Pharmacokinetics of ethionamide in children.
abstract: Ethionamide (ETH), a second-line antituberculosis drug, is frequently used in treating childhood tuberculosis. Data supporting ETH dose recommendations in children are limited. The aim of this study was to determine the pharmacokinetic parameters for ETH in children on antituberculosis treatment including ETH. ETH serum levels were prospectively assessed in 31 children in 3 age groups (0 to 2 years, 2 to 6 years, and 6 to 12 years). Within each age group, half received rifampin (RMP). Following an oral dose of ETH (15 to 20 mg/kg of body weight), blood samples were collected at 0, 1, 2, 3, 4, and 6 h following 1 and 4 months of ETH therapy. The maximum serum concentration (C(max)), time to C(max) (T(max)), and area under the time-concentration curve from 0 to 6 h (AUC(0-6)) were calculated. Younger children were exposed to lower ETH concentrations than older children at the same mg/kg body weight dose. Age correlated significantly with the AUC after both 1 month (r = 0.50, P = 0.001) and 4 months (r = 0.63, P = 0.001) of therapy. There was no difference in the AUC or C(max) between children receiving concomitant treatment with RMP and those who did not. Time on treatment did not influence the pharmacokinetic parameters of ETH following 1 and 4 months of therapy. HIV infection was associated with lower ETH exposure. In conclusion, ETH at an oral dose of 15 to 20 mg/kg results in sufficient serum concentrations compared to current adult recommended levels in the majority of children across all age groups. ETH levels were influenced by young age and HIV status but were not affected by concomitant RMP treatment and duration of therapy.
authors.affiliation: Department of Paediatric Pneumology and Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany. steffi.thee@googlemail.com
authors.forename: S
authors.initials: S
authors.lastname: Thee
authors.forename: H I
authors.initials: HI
authors.lastname: Seifart
authors.forename: B
authors.initials: B
authors.lastname: Rosenkranz
authors.forename: A C
authors.initials: AC
authors.lastname: Hesseling
authors.forename: K
authors.initials: K
authors.lastname: Magdorf
authors.forename: P R
authors.initials: PR
authors.lastname: Donald
authors.forename: H S
authors.initials: HS
authors.lastname: Schaaf
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005000:Ethionamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007223:Infant; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
chemical_list: D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D005000:Ethionamide; D012293:Rifampin