Awadzi K, Adjepon-Yamoah K K, Edwards G, Orme M L, Breckenridge A M, Gilles H M
Br J Clin Pharmacol. 1986 Jun;21(6):669-76. doi: 10.1111/j.1365-2125.1986.tb05232.x.
Twenty-one patients with moderate to heavy infections with O. volvulus were treated with 25 mg of diethylcarbamazine (DEC) citrate twice daily for 10 days. In 11 patients the urine was made alkaline with sodium bicarbonate, 2 g, administered 6 hourly for three doses daily beginning 1 day before DEC was started and continued throughout the DEC therapy. Ten patients served as controls. The mean pre-dose plasma DEC concentration during treatment and the mean plasma DEC half-life were significantly higher in bicarbonate treated patients as compared to controls. Total urinary excretion of DEC was significantly less in the bicarbonate treated group than in controls. Mean overall total reaction was higher in bicarbonate-treated patients but the difference was not significant. The bicarbonate-treated group achieved a significantly greater reduction in skin microfilarial counts than the control group as assessed 1 week after completion of therapy, but there was little difference at 1 month. Microfilarial killing was associated with microfilarial mobilisation, alteration in peripheral leucocytes and elevation in serum aminotransferases in both groups. There was no effect of DEC on the number of adult worms recovered in nodules removed at the end of the therapy. This study indicates that moderate urinary alkalinisation alters the kinetics of DEC and the therapeutic response. However the severity of clinical reaction coupled with the inadequate level of microfilarial killing achieved make it unlikely that manipulation of urinary pH will be of practical value in onchocerciasis chemotherapy.
21例中度至重度盘尾丝虫感染患者接受了枸橼酸乙胺嗪(DEC)治疗,剂量为25mg,每日两次,共10天。11例患者服用2g碳酸氢钠使尿液碱化,从开始服用DEC前1天起,每6小时给药1次,每日3剂,在整个DEC治疗期间持续给药。10例患者作为对照。与对照组相比,接受碳酸氢钠治疗的患者在治疗期间的平均给药前血浆DEC浓度和平均血浆DEC半衰期显著更高。碳酸氢钠治疗组的DEC总尿排泄量显著低于对照组。碳酸氢钠治疗患者的平均总体总反应较高,但差异不显著。在治疗完成1周后评估,碳酸氢钠治疗组的皮肤微丝蚴计数显著低于对照组,但在1个月时差异不大。两组的微丝蚴杀灭均与微丝蚴动员、外周白细胞改变和血清转氨酶升高有关。DEC对治疗结束时取出的结节中回收的成虫数量没有影响。这项研究表明,适度的尿液碱化会改变DEC的动力学和治疗反应。然而,临床反应的严重程度加上微丝蚴杀灭水平不足,使得调节尿液pH值在盘尾丝虫病化疗中不太可能具有实际价值。