Sundar S, Sinha P R, Agrawal N K, Srivastava R, Rainey P M, Berman J D, Murray H W, Singh V P
Kala-Azar Medical Research Center, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. shyam/
Am J Trop Med Hyg. 1998 Jul;59(1):139-43. doi: 10.4269/ajtmh.1998.59.139.
In India, sodium antimony gluconate is the drug of choice for kala-azar. Due to increasing unresponsiveness to this drug in the current epidemic that began in the early 1970s, daily doses of 20 mg/kg/day for 30 days or more is recommended as opposed to the 10 mg/kg/day dose for 6-10 days used in the past. Of the 130-150 patients treated annually at our center with locally made sodium antimony gluconate, serious cardiotoxicity has occurred in less than 10%. During April 1995 at the University Hospital in Varanasi, we encountered life-threatening cardiotoxicity after 3-28 days of therapy in each of the eight patients being treated with a new lot of this drug made by a different manufacturer. Of the eight patients, six each developed congestive heart failure and/or prolongation of the corrected QT interval (QTc), and three died as a direct consequence of drug-induced toxicities. In three instances, the life-threatening complications occurred with a cumulative dose of less than 300 mg/kg. In patients with prolonged QTc, ventricular premature beats and ventricular tachycardia were recorded; in one patient, the ventricular tachycardia progressed to torsade de pointes, culminating in ventricular fibrillation and death. Since switching to different lots of this drug, we have not seen further clustering of dangerous cardiotoxicity. The antimony content of the implicated drug was comparable with that in lots from other manufacturers that did not show overt toxicity, but the osmolarity was approximately 300 mOsm/L higher. The simple technique of measuring of osmolarity may help identify inappropriately manufactured drug.
在印度，葡萄糖酸锑钠是治疗黑热病的首选药物。由于自20世纪70年代初开始的当前疫情中对该药物的无反应性增加，建议每日剂量为20mg/kg/天，持续30天或更长时间，而过去使用的剂量为10mg/kg/天，持续6 - 10天。在我们中心每年用本地生产的葡萄糖酸锑钠治疗的130 - 150名患者中，严重心脏毒性的发生率不到10%。1995年4月，在瓦拉纳西的大学医院，我们在使用不同制造商生产的该药物新批次治疗的8名患者中，有8名在治疗3 - 28天后出现了危及生命的心脏毒性。在这8名患者中，各有6名出现充血性心力衰竭和/或校正QT间期（QTc）延长，3名因药物诱导的毒性直接死亡。在3例中，累积剂量小于300mg/kg时就出现了危及生命的并发症。在QTc延长的患者中，记录到室性早搏和室性心动过速；在1例患者中，室性心动过速进展为尖端扭转型室速，最终导致心室颤动和死亡。自从改用该药物的不同批次后，我们没有再看到危险心脏毒性的进一步聚集。有问题的药物中的锑含量与其他未显示明显毒性的制造商生产的批次相当，但渗透压大约高300mOsm/L。测量渗透压的简单技术可能有助于识别生产不当的药物。
