TITLE

Pharmacokinetics of Antimony in Children Treated for Leishmaniasis with Meglumine Antimoniate

AUTHOR(S)
Cruz, Adriana; Rainey, Petrie M.; Herwaldt, Barbara L.; Stagni, Grazia; Palacios, Ricardo; Trujillo, Rodolfo; Saravia, Nancy G.
PUB. DATE
February 2007
SOURCE
Journal of Infectious Diseases;2/15/2007, Vol. 195 Issue 4, p602
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
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 (AUC0-24) in plasma. Results. Children (vs. adults) who received 20 mg/kg had a 42% lower AUC0-24 (mean ± SE, vs. 111 ± 7 vs. 190 ± 10 mg × 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 ± 0.006 L/h/kg; P < .001). The 30 mg/kg dose in children increased the AUC0-24 to 164 ± 10 mg × 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.
ACCESSION #
28447101

 

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