Background: Sulphadoxine-pyrimethamine, in combination with artesunate or amodiaquine, is recommended for\r\nthe treatment of uncomplicated malaria and is being evaluated for intermittent preventive treatment. Yet, limited\r\ndata is available on pharmacokinetic interactions between these drugs.\r\nMethods: In a randomized controlled trial, children aged 6-59 months with uncomplicated falciparum malaria,\r\nreceived either one dose of sulphadoxine-pyrimethamine alone (SP), one dose of SP plus three daily doses of\r\namodiaquine (SP) or one dose of SP plus 3 daily doses of artesunate (SP). Exactly 100 �µl of capillary blood\r\nwas collected onto filter paper before drug administration at day 0 and at days 1, 3, 7, 14, 21 and 28 after drug\r\nadministration for analysis of sulphadoxine and pyrimethamine pharmacokinetic parameters.\r\nResults: Fourty, 38 and 31 patients in the SP, SP and SP arms, respectively were included in this study.\r\nThe concentrations on day 7 (that are associated with therapeutic efficacy) were similar between the SP, SP\r\nand SP treatment arms for sulphadoxine (median [IQR] 35.25 [27.38-41.70], 34.95 [28.60-40.85] and 33.40 [24.63-\r\n44.05] �µg/mL) and for pyrimethamine (56.75 [46.40-92.95], 58.75 [43.60-98.60] and 59.60 [42.45-86.63] ng/mL). There\r\nwere statistically significant differences between the pyrimethamine volumes of distribution (4.65 [3.93-6.40], 4.00\r\n[3.03-5.43] and 5.60 [4.40-7.20] L/kg; p = 0.001) and thus elimination half-life (3.26 [2.74 -3.82], 2.78 [2.24-3.65] and\r\n4.02 [3.05-4.85] days; p < 0.001). This study confirmed the lower SP concentrations previously reported for young\r\nchildren when compared with adult malaria patients.\r\nConclusion: Despite slight differences in pyrimethamine volumes of distribution and elimination half-life, these\r\ndata show similar exposure to SP over the critical initial seven days of treatment and support the current use of SP\r\nin combination with either AQ or AS for uncomplicated falciparum malaria treatment in young Malian children.
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