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- W2072914025 abstract "The multiple-dose kinetics of a daily dose of proguanil (200 mg) coadministered with dapsone (10 mg) was investigated in 6 healthy adult male volunteers. The kinetics of dapsone (DDS), monoacetyldapsone (MADDS), proguanil (PROG) and its active metabolite cycloguanil (CYCLO) were derived from plasma drug concentrations after the last maintenance dose. The following kinetic parameters (mean values) were estimated for DDS and PROG, respectively: maximum concentration (Cmax) = 285 and 151 ng/ml, minimum concentration (Cmin) = 125 and 31 ng/ml, elimination half-life (t.½) = 23.3 and 18.3 h, plasma clearance (CI) = 0.032 and 1.27 1/h/kg and apparent volume of distribution (Vss) = 1.05 and 33.32 1/kg. The Cmax, Cmin and t½ of CYCLO were 56 ng/ml, 17 ng/ml and 15.0 h, respectively. The antimalarial activity of the proguanil/ dapsone combination was assessed in vitro by measuring the inhibition of re-invasion of two Plasmodium falciparum isolates grown in the presence of volunteers’sera. Both FC-27 [chloroquine (CQ) and pyrimethamine (PYR)-sensitive] and Kl (CQ- and PYR-resistant) isolates were completely inhibited by the drug combination at steady-state concentrations. These findings suggest that the drug regimen may be effective against drug-resistant falciparum malaria." @default.
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- W2072914025 date "1990-01-01" @default.
- W2072914025 modified "2023-10-03" @default.
- W2072914025 title "Multiple-Dose Kinetics in Healthy Volunteers and in vitro Antimalarial Activity of Proguanil plus Dapsone" @default.
- W2072914025 doi "https://doi.org/10.1159/000238763" @default.
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