Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Am J Ther. 2012 Sep;19(5):338-45. doi: 10.1097/MJT.0b013e3181baf266.
Sulfadoxine (SDX)-pyrimethamine is currently recommended as a partner drug with artesunate in the chemotherapy of malaria. However, information on pharmacokinetic disposition of SDX-pyrimethamine in children is limited. Efforts in this study were thus devoted to evaluation of pharmacokinetic disposition of SDX using high-pressure liquid chromatographic techniques and effects of pharmacokinetic variability on treatment outcome in Nigerian children with falciparum malaria. The blood concentration profile of SDX was similar in patients whose infection responded to treatment and those who failed treatment; mean SDX concentration values were similar for day 3 (179 vs 157 μg/mL, P = 0.734), day 7 (84 vs 51 μg/mL, P = 0.365), and day 14 (50 vs 14 μg/mL, P = 0.151). Extent of exposure (area under the curve) to SDX was also similar in the patients (1196 vs 1013 μg d/mL, P = 0.561). Pearson's correlation, showed significant correlation between area under the curve and D3 or D7 concentration of SDX (P = 0.001, r = 0.702 or P = 0.001, r = 0.835, respectively). Age-stratified analysis showed that SDX concentrations were significantly higher in older children (older than 5 years); the mean maximum concentration (125 vs 295 μg/mL, P = 0.001), extent of exposure (812 vs 1562 μg d/mL, P = 0.001), day 3 concentration (98 vs 250 μg/mL, P = 0.001), and day 7 concentration (54 vs 128 μg/mL, P = 0.007) were higher. The study revealed no differences in posttreatment blood SDX concentrations in patients who responded to treatment and those who failed to respond to treatment. Furthermore, there was an age-related pharmacokinetic variability of SDX in the group of children studied with potential impact on treatment outcome.
磺胺多辛-乙胺嘧啶目前被推荐作为青蒿琥酯治疗疟疾的联合用药。然而，有关儿童磺胺多辛-乙胺嘧啶药代动力学特征的信息有限。因此，本研究致力于采用高压液相色谱技术评价磺胺多辛的药代动力学特征，并研究其在尼日利亚儿童恶性疟中的药代动力学变异性对治疗效果的影响。磺胺多辛血药浓度曲线在治疗有效和治疗失败的患者中相似；第 3 天（179 与 157μg/ml，P=0.734）、第 7 天（84 与 51μg/ml，P=0.365）和第 14 天（50 与 14μg/ml，P=0.151）的平均磺胺多辛浓度值相似。磺胺多辛的暴露程度（曲线下面积）在患者中也相似（1196 与 1013μg·d/ml，P=0.561）。Pearson 相关分析显示，磺胺多辛的曲线下面积与第 3 天或第 7 天的磺胺多辛浓度之间存在显著相关性（P=0.001，r=0.702 或 P=0.001，r=0.835）。年龄分层分析显示，磺胺多辛浓度在年龄较大的儿童（5 岁以上）中显著较高；最大浓度（125 与 295μg/ml，P=0.001）、暴露程度（812 与 1562μg·d/ml，P=0.001）、第 3 天浓度（98 与 250μg/ml，P=0.001）和第 7 天浓度（54 与 128μg/ml，P=0.007）较高。研究结果显示，治疗有效的患者与治疗失败的患者的治疗后血磺胺多辛浓度无差异。此外，在所研究的儿童组中，磺胺多辛的药代动力学存在年龄相关性变异性，可能对治疗效果产生影响。
