Publication: Efficacy and pharmacokinetics of atovaquone and proguanil in children with multidrug-resistant Plasmodium falciparum malaria
Issued Date
1998-01-01
Resource Type
ISSN
00359203
Other identifier(s)
2-s2.0-13144275246
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Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Transactions of the Royal Society of Tropical Medicine and Hygiene. Vol.92, No.2 (1998), 201-206
Suggested Citation
A. Sabchareon, P. Attanath, P. Phanuaksook, P. Chanthavanich, Y. Poonpanich, D. Mookmanee, T. Chongsuphajaisiddhi, B. M. Sadler, Z. Hussein, C. J. Canfield, D. B.A. Hutchinson Efficacy and pharmacokinetics of atovaquone and proguanil in children with multidrug-resistant Plasmodium falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene. Vol.92, No.2 (1998), 201-206. doi:10.1016/S0035-9203(98)90749-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/18427
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Title
Efficacy and pharmacokinetics of atovaquone and proguanil in children with multidrug-resistant Plasmodium falciparum malaria
Abstract
A trial was conducted in 32 Thai children with uncomplicated multidrug-resistant falciparum malaria to assess the efficacy, safety and pharmacokinetics of atovaquone and proguanil; plasma concentrations of atovaquone, proguanil and its metabolite, cycloguanil, were measured in a subset of 9 children. The children received atovaquone (17 mg/kg/d for 3 d) plus proguanil (7 mg/kg/d for 3 d). Twenty-six children who had only Plasmodium falciparum infection and remained in hospital for 28 d were assessed for drug efficacy. The combination regimen produced a cure rate of 100%. Parasite and fever clearance times were 47 h (range 8-75) and 50 h (range 7-111), respectively. Atovaquone and proguanil were rapidly absorbed, with median time to peak concentrations of 6 h (range 6-24) and 6 h (range 6-12), respectively. Peak concentrations of cycloguanil were achieved between 6 and 12 h (median 6) after administration of proguanil. Mean peak plasma concentration of atovaquone on day 3 was 5.1 μg/mL (SD = 2.1). The day 3 mean peak plasma concentration of proguanil was 306 ng/mL (SD = 108) compared with 44.3 ng/mL (SD = 27.3) for cycloguanil. Mean values for the AUC (area under plasma concentration-time curve) were 161.8 μg/mL·h (SD = 126.9) for atovaquone, 4646 ng/mL·h (SD = 1226) for proguanil, and 787 ng/mL·h (SD = 397) for cycloguanil. Terminal elimination half-lives of atovaquone, proguanil and cycloguanil were estimated as 31.8 h (SD = 8.9), 14.9 h (SD = 3.3) and 14.6 h (SD = 2.6), respectively. No major adverse effect was attributable to the study drugs. Atovaquone/proguanil combination is safe and highly effective, and should be especially valuable for treatment of multidrug-resistant falciparum malaria.