title: Safety and pharmacokinetics of urtoxazumab, a humanized monoclonal antibody, against Shiga-like toxin 2 in healthy adults and in pediatric patients infected with Shiga-like toxin-producing Escherichia coli.
abstract: Shiga-like toxin-producing Escherichia coli (STEC) infection causes diarrhea, which is often bloody and which can result in potentially life-threatening hemolytic-uremic syndrome (HUS). Urtoxazumab, a humanized monoclonal antibody directed against the Shiga-like toxin 2 (Stx2) produced by STEC, has been developed as a promising agent for the prevention of HUS. Single randomized, intravenous, double-blind, placebo-controlled doses of urtoxazumab were administered to assess its safety and pharmacokinetics in healthy adults (0.1 to 3.0 mg/kg of body weight) and STEC-infected pediatric patients (1.0 and 3.0 mg/kg). No dose-related safety trends were noted, nor were antiurtoxazumab antibodies detected. The disposition of urtoxazumab showed a biexponential decline, regardless of the dose. In healthy adults, the mean terminal elimination half-life was consistent across the dose groups and ranged from 24.6 days (3.0-mg/kg dose group) to 28.9 days (0.3-mg/kg dose group). The mean maximum serum drug concentration (C(max)) ranged from 2.6 microg/ml at 0.1 mg/kg to 71.7 microg/ml at 3.0 mg/kg. The disposition of urtoxazumab following the administration of doses of 1.0 and 3.0 mg/kg in pediatric patients showed mean C(max)s of 19.6 and 56.1 microg/ml, respectively. Urtoxazumab was well tolerated, appears to be safe at doses of up to 3.0 mg/kg, and is a potential candidate for the prevention of HUS in pediatric patients.
authors.affiliation: Hospital de Niños Dr. Ricardo Gutiérrez, Guido 2676, Piso 10, Buenos Aires 1425, Argentina. eduardoluislopez@fibertel.com.ar
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: López
authors.forename: Maria M
authors.initials: MM
authors.lastname: Contrini
authors.forename: Eduardo
authors.initials: E
authors.lastname: Glatstein
authors.forename: Silvia
authors.initials: S
authors.lastname: González Ayala
authors.forename: Roberto
authors.initials: R
authors.lastname: Santoro
authors.forename: Daniel
authors.initials: D
authors.lastname: Allende
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ezcurra
authors.forename: Eduardo
authors.initials: E
authors.lastname: Teplitz
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Koyama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sato
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Sakai
authors.forename: Satoru
authors.initials: S
authors.lastname: Hoshide
authors.forename: Keiji
authors.initials: K
authors.lastname: Komoriya
authors.forename: Takuya
authors.initials: T
authors.lastname: Morita
authors.forename: Ronald
authors.initials: R
authors.lastname: Harning
authors.forename: Sheldon
authors.initials: S
authors.lastname: Brookman
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000906:Antibodies / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004926:Escherichia coli / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D022641:Shiga Toxin 2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000906:Antibodies; D000911:Antibodies, Monoclonal; D022641:Shiga Toxin 2