Pharmacokinetics of antimony in children treated for leishmaniasis with meglumine antimoniate

Pharmacokinetics of antimony in children treated for leishmaniasis with meglumine antimoniate

Author Cruz, Adriana Taveira da Autor UNIFESP Google Scholar
Rainey, Petrie M. Google Scholar
Herwaldt, Barbara L. Google Scholar
Stagni, Grazia Google Scholar
Palacios, Ricardo Google Scholar
Trujillo, Rodolfo Autor UNIFESP Google Scholar
Saravia, Nancy G. Google Scholar
Institution Ctr Int Entrenamiento & Invest Med
Univ Washington
Ctr Dis Control & Prevent
Long Isl Univ
Universidade Federal de São Paulo (UNIFESP)
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, vs. 111 +/- 7 190 +/- 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.
Language English
Date 2007-02-15
Published in Journal of Infectious Diseases. Chicago: Univ Chicago Press, v. 195, n. 4, p. 602-608, 2007.
ISSN 0022-1899 (Sherpa/Romeo, impact factor)
Publisher Univ Chicago Press
Extent 602-608
Access rights Closed access
Type Article
Web of Science ID WOS:000243565800020

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