期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 59, 期 9, 页码 5114-5122出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.04957-14
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Artemisinin-based combination therapies (ACTs) have been adopted by most African countries, including Nigeria, as first-line treatments for uncomplicated falciparum malaria. Fixed-dose combinations of these ACTs, amodiaquine-artesunate (FDC AQAS) and artemether-lumefantrine (AL), were introduced in Nigeria to improve compliance and achieve positive outcomes of malaria treatment. In order to achieve clinical success with AQAS, we developed and validated a simple and sensitive high-performance liquid chromatography (HPLC) method with UV detection for determination of amodiaquine (AQ) and desethylamodiaquine (DAQ) in plasma using liquid-liquid extraction of the drugs with diethyl ether following protein precipitation with acetonitrile. Chromatographic separation was achieved using an Agilent Zorbax C-18 column and a mobile phase consisting of distilled water-methanol (80: 20 [vol/vol]) with 2% (vol/vol) triethylamine, pH 2.2, at a flow rate of 1 ml/min. Calibration curves in spiked plasma were linear from 100 to 1,000 ng/ml (r > 0.99) for both AQ and DAQ. The limit of detection was 1 ng (sample size, 20 mu l). The intra-and interday coefficients of variation at 150, 300, and 900 ng/ml ranged from 1.3 to 4.8%, and the biases were between 6.4 and 9.5%. The mean extraction recoveries of AQ and DAQ were 80.0% and 68.9%, respectively. The results for the pharmacokinetic parameters of DAQ following oral administration of FDC AQAS (612/200 mg) for 3 days in female and male patients with uncomplicated falciparum malaria showed that the maximum plasma concentrations (C-max) (740 +/- 197 versus 767 +/- 185 ng/ml), areas under the plasma concentration-time curve (AUC) (185,080 +/- 20,813 versus 184,940 +/- 16,370 h.ng/ml), and elimination half-life values (T-1/2) (212 +/- 1.14 versus 214 +/- 0.84 h) were similar (P > 0.05).
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