title: Pharmacokinetics and safety profile of tigecycline in children aged 8 to 11 years with selected serious infections: a multicenter, open-label, ascending-dose study.
abstract: BACKGROUND
  Tigecycline, a broad-spectrum antibiotic used for treating serious bacterial infections in adults, may be suitable for pediatric use once an appropriate dosage is determined.
  
  
  OBJECTIVE
  The aim of this study was to assess the pharmacokinetic (PK) properties, safety profile, and descriptive efficacy of tigecycline.
  
  
  METHODS
  In this Phase II, multicenter, open-label clinical trial, children aged 8 to 11 years with community-acquired pneumonia (CAP), complicated intra-abdominal infection (cIAI), or complicated skin and skin structure infections (cSSSI) were administered tigecycline 0.75, 1, or 1.25 mg/kg.
  
  
  RESULTS
  A total of 58 patients received ≥ 1 dose of tigecycline (31 boys; 44 white; mean age, 10 years; mean weight, 35 kg); 47 had data from samples available for PK analysis. The mean (SD) PK values were: C(max), 1899 (2954) ng/mL; T(max), 0.56 (0.18) hour; between-dose AUC, 2833 (1557) ng · h/mL; weight-normalized clearance, 0.503 (0.293) L/h/kg; and Vd(ss), 4.88 (4.84) L/kg. Overall clinical cure rates at test-of-cure were 94% (16/17), 76% (16/21), and 75% (15/20) in the 0.75-, 1-, and 1.25-mg/kg cohorts, respectively. The rates of protocol violations were higher in the 1- and 1.25-mg/kg groups, resulting in higher proportions of indeterminate clinical cure assessments relative to the 0.75-mg/kg cohort (19% and 15% vs 0%). The most frequent adverse event was nausea, which occurred in 50% of patients overall (29/58) and the prevalence of which was significantly higher in the 1.25-mg/kg group versus the 0.75-mg/kg group (65% vs 18%; P = 0.007). Pharmacodynamic simulations using MIC data from an ongoing microbiological surveillance trial predicted that a dosage of 1.2 mg/kg q12h would lead to therapeutic target attainment levels of up to 82% for the target AUC(0-24)/MIC ratios.
  
  
  CONCLUSIONS
  A tigecycline dosage of ∼1.2 mg/kg q12h may represent the most appropriate dosage for subsequent evaluation in Phase III clinical trials in children aged 8 to 11 years with selected serious bacterial infections. ClinicalTrials.gov identifier: NCT00488345.
authors.affiliation: Pfizer formerly Clinical Research, Wyeth Research, Collegeville, Pennsylvania 19426, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Purdy
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jouve
authors.forename: Jean Li
authors.initials: JL
authors.lastname: Yan
authors.forename: Ivana
authors.initials: I
authors.lastname: Balter
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dartois
authors.forename: C Angel
authors.initials: CA
authors.lastname: Cooper
authors.forename: Joan
authors.initials: J
authors.lastname: Korth-Bradley
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001424:Bacterial Infections / Q000188:drug therapy*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008911:Minocycline / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline