title: Pharmacokinetics of antimony in children treated for leishmaniasis with meglumine antimoniate.
abstract: BACKGROUND
  In some settings, the response to pentavalent antimonial therapy for leishmaniasis may be lower in children than in adults. We hypothesized that there are age-dependent pharmacokinetic differences of potential clinical relevance.
  
  
  METHODS
  We compared the pharmacokinetics of antimony (Sb) in adults and 2 groups of children 3-6 years old who had cutaneous leishmaniasis treated with intramuscular meglumine antimoniate. Adults (n=9) and the first group of children (n=9) received 20 mg Sb/kg/day for 20 days; the second group of children (n=6) received 20 mg Sb/kg for 19 days and 30 mg Sb/kg on day 20. Drug exposure was assessed by the area under the 24-h time-concentration curve (AUC(0-24)) in plasma.
  
  
  RESULTS
  Children (vs. adults) who received 20 mg/kg had a 42% lower AUC(0-24) (mean +/- SE, 111+/-7 vs. 190+/-10 mg x h/L, compared with adults; P<.001), a 16% lower peak concentration (32.7+/-0.9 vs. 38.8+/-2.1 mg/L; P=.04), and a 75% higher weight-adjusted clearance (0.185+/-0.013 vs. 0.106+/-0.006 L/h/kg; P<.001). The 30 mg/kg dose in children increased the AUC(0-24) to 164+/-10 mg x h/L and the peak concentration to 43.8+/-2.3 mg/L.
  
  
  CONCLUSIONS
  Drug exposure is significantly lower in children than in adults treated with the same weight-adjusted regimen of meglumine antimoniate, which primarily stems from a higher antimony clearance rate.
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Medicas, Cali, AA 5390, Colombia.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cruz
authors.forename: Petrie M
authors.initials: PM
authors.lastname: Rainey
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Herwaldt
authors.forename: Grazia
authors.initials: G
authors.lastname: Stagni
authors.forename: Ricardo
authors.initials: R
authors.lastname: Palacios
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Trujillo
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Saravia
mesh_terms: D000328:Adult; D000965:Antimony / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000627:therapeutic use*; D000077485:Meglumine Antimoniate; D008657:Metabolic Clearance Rate; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D010949:Plasma / Q000737:chemistry
chemical_list: D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony