title: A review of the use of ethionamide and prothionamide in childhood tuberculosis.
abstract: Ethionamide (ETH) and prothionamide (PTH), both thioamides, have proven efficacy in clinical studies and form important components for multidrug-resistant tuberculosis treatment regimens and for treatment of tuberculous meningitis in adults and children. ETH and PTH are pro-drugs that, following enzymatic activation by mycobacterial EthA inhibit InhA, a target shared with isoniazid (INH), and subsequently inhibit mycolic acid synthesis of Mycobacterium tuberculosis. Co-resistance to INH and ETH is conferred by mutations in the mycobacterial inhA promoter region; mutations in the ethA gene often underlie ETH and PTH monoresistance. An oral daily dose of ETH or PTH of 15-20 mg/kg with a maximum daily dose of 1000 mg is recommended in children to achieve adult-equivalent serum concentrations shown to be efficacious in adults, although information on optimal pharmacodynamic targets is still lacking. Gastrointestinal disturbances, and hypothyroidism during long-term therapy, are frequent adverse effects observed in adults and children, but are rarely life-threatening and seldom necessitate cessation of ETH therapy. More thorough investigation of the therapeutic effects and toxicity of ETH and PTH is needed in childhood TB while child-friendly formulations are needed to appropriately dose children.
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Department of Paediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Germany. Electronic address: Stephanie.thee@charite.de.
authors.forename: S
authors.initials: S
authors.lastname: Thee
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: A J
authors.initials: AJ
authors.lastname: Garcia-Prats
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: P R
authors.initials: PR
authors.lastname: Donald
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: A C
authors.initials: AC
authors.lastname: Hesseling
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
authors.forename: H S
authors.initials: HS
authors.lastname: Schaaf
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D004339:Drug Compounding; D054796:Drug Dosage Calculations; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005000:Ethionamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D011515:Prothionamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011515:Prothionamide; D005000:Ethionamide
keywords: Children; Ethionamide; Pharmacokinetics; Prothionamide; Safety; Thioamides; Tuberculosis treatment