Iribhogbe Osede I, Emmanuel Igue, Odianosen Marylove
Department of Pharmacology and Therapeutics.
Department of Human Physiology College of Medicine, Ambrose Alli University Ekpoma, Edo State, Nigeria.
Clin Pharmacol. 2017 May 9;9:45-54. doi: 10.2147/CPAA.S131351. eCollection 2017.
A comparative clinical study was conducted to evaluate the safety and tolerability of two commonly used fixed dose artemisinin-based combinations for the treatment of uncomplicated malaria in the second and third trimester of pregnancy. To achieve this, a total of 155 participants were recruited for the study. Eighty of these were drawn from pregnant women who came for routine antenatal care while 40 nonpregnant participants were recruited from apparently healthy females in the community. Eighty pregnant participants with uncomplicated malaria were randomized into artesunate/amodiaquine (AA) and artemether/lumefantrine (AL) treatment arms while 40 nonpregnant and 35 nonmalarious pregnant women were used as control. The interventional groups received standard fixed dose combinations of AA (100/270 mg) daily or AL (20/120 mg) twice daily for 3 days. Blood samples were collected on day 4 and patients were followed-up closely to ascertain the safety of the drugs. The study showed a significant (<0.0001) elevation of alkaline phosphatase in the AA and AL group compared to the nonpregnant control and a significant (<0.05) elevation of alanine transaminase and aspartate transaminase level in the AL combination group when compared with the AA group. The elevated hepatic enzymes were within the normal range for pregnancy and were not clinically significant. Adverse event rate was higher in the AA group (n=28 [70%]) when compared to the AL group (n=4 [10%]) although the drugs were well-tolerated in both treatment arms. In conclusion, the use of these combinations is safe in the second and third trimester of pregnancy. However, we recommend active pharmacovigilance and spontaneous drug reporting of the agents in order to continuously monitor safety in the vastly heterogeneous population.
开展了一项比较临床研究，以评估两种常用的固定剂量青蒿素类复方药物在治疗妊娠中期和晚期单纯性疟疾时的安全性和耐受性。为此，共招募了155名参与者进行该研究。其中80名来自前来进行常规产前检查的孕妇，另外40名非孕妇参与者则从社区中看似健康的女性中招募。80名患有单纯性疟疾的孕妇被随机分为青蒿琥酯/阿莫地喹（AA）和蒿甲醚/本芴醇（AL）治疗组，同时将40名非孕妇和35名未患疟疾的孕妇作为对照组。干预组分别接受标准固定剂量的AA（100/270毫克）每日一次或AL（20/120毫克）每日两次，持续3天。在第4天采集血样，并对患者进行密切随访以确定药物的安全性。研究表明，与非孕妇对照组相比，AA组和AL组的碱性磷酸酶显著升高（<0.0001），与AA组相比，AL复方组的丙氨酸转氨酶和天冬氨酸转氨酶水平显著升高（<0.05）。升高的肝酶在妊娠正常范围内，无临床意义。AA组的不良事件发生率（n = 28 [70%]）高于AL组（n = 4 [10%]），尽管两个治疗组对药物的耐受性都良好。总之，这些复方药物在妊娠中期和晚期使用是安全的。然而，我们建议对这些药物进行积极的药物警戒和自发报告，以便在差异极大的人群中持续监测安全性。
