Pharmacokinetics of antimony in children treated for leishmaniasis with meglumine antimoniate.
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.
Cruz
Adriana
A
Centro Internacional de Entrenamiento e Investigaciones Medicas, Cali, AA 5390, Colombia.
Rainey
Petrie M
PM
Herwaldt
Barbara L
BL
Stagni
Grazia
G
Palacios
Ricardo
R
Trujillo
Rodolfo
R
Saravia
Nancy G
NG
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
D009942:Organometallic Compounds; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000965:Antimony