Filaricidal efficacy of anthelmintically active cyclodepsipeptides
Filaricidal efficacy of anthelmintically active cyclodepsipeptides
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DOI：
10.1016/s0020-7519(01)00263-6
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发表时间：
2001-11-01
影响因子：
4
通讯作者：
von Samson-Himmelstjerna, G
中科院分区：
文献类型：
--
作者：
Zahner, H;Taubert, A;von Samson-Himmelstjerna, G
PF 1022A。一种新的具有驱虫活性的环缩酚酸肽和PF 1022 A的半合成衍生物Bay 44-4400在感染了斜纹软蜱（Litomosoides sigmodontis）、葡萄棘唇线虫（Acanthocheilonema viteae）和马来丝虫（Brugia malayi）的贝壳乳鼠（Mastomys concha）中测试杀丝虫效力。母体化合物PF 1022 A在L. sigmodontis和B.马来人感染的动物。连续几天口服5 x 100 mg/kg剂量仅导致微丝蚴血症水平暂时降低。相比之下，Bay 44-4400在单次口服、皮下和皮下施用（点涂）剂量中对所有三种微丝蚴都非常有效。给药后3天和7天确定的最小有效剂量（MED，降低寄生虫密度≥ 95%）分别为3.125-6.25和6.25-12.5 mg/kg。使用制剂上的斑点，剂量为6.25 mg/kg（L. sigmodontis）、12.5mg/kg（A. viteae）和25 mg/kg（B.马来人）导致微丝蚴血症水平降低大于或等于95%，直至第56天。以单次给药后的最小治疗剂量（MCD，56天内消除成虫寄生虫>95%）确定的杀成虫作用仅限于A。viteae（MCD，100 mg/kg，与给药途径无关）。重复经口给药（100 mg/kg，连续5天）杀死所有成虫。乙状窦但不影响B。马来语。然而，6.25和25 mg/kg的单次剂量导致L的宫内阶段的严重病理学改变。sigmodontis和B.马来人，分别。这些改变可能是持久减少微丝蚴血症的原因，即使不能达到治疗效果。(C)2001年澳大利亚寄生虫学会由Elsevier Science Ltd.出版，版权所有。
PF 1022A. a novel anthelmintically active cyclodepsipeptide, and Bay 44-4400, a semisynthetic derivative of PF 1022A were tested for filaricidal efficacy in Mastomys concha infected with Litomosoides sigmodontis, Acanthocheilonema viteae and Brugia malayi. The parent compound PF 1022A showed limited anti-filarial efficacy in L. sigmodontis and B. malayi infected animals. Oral doses of 5 x 100 mg/kg on consecutive days caused only a temporary decrease of microfilariaemia levels. By contrast, Bay 44-4400 was highly effective against microfilariae of all three species in single oral, subcutaneous and cutaneously applied (spot on) doses. Minimum effective doses (MED, reducing parasitaemia density by greater than or equal to 95%) determined 3 and 7 days after treatment were 3.125-6.25 and 6.25-12.5 mg/kg, respectively. Using the spot on formulation, doses of 6.25 mg/kg (L. sigmodontis), 12.5 mg/kg (A. viteae) and 25 mg/kg (B. malayi) were required to cause reductions of microfilaraemia levels by greater than or equal to 95% until day 56. Adulticidal effects, determined as minimum curative doses (MCD, eliminating adult parasites within 56 days by >95%) after single dose treatment were limited to A. viteae (MCD, 100 mg/kg independent of the route of administration). Repeated oral treatment (100 mg/kg on 5 consecutive days) killed all adult L. sigmodontis but did not affect B. malayi. However, single doses of 6.25 and 25 mg/kg resulted in severe pathological alterations of intrauterine stages of L. sigmodontis and B. malayi, respectively. These alterations may be responsible for long-lasting reductions of microfilaraemia even when curative effects could not be achieved. (C) 2001 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.