Pharmacokinetics of Antimony in Children Treated for Leishmaniasis with Meglumine Antimoniate

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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, 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 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.

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