Filaricidal efficacy of anthelmintically active cyclodepsipeptides

PF 1022A. a novel anthelmintically active cyclodepsipeptide, and Bay 44-440 0, a semisynthetic derivative of PF 1022A were tested for filaricidal effic acy in Mastomys concha infected with Litomosoides sigmodontis, Acanthocheil onema viteae and Brugia malayi. The parent compound PF 1022A showed limited anti-filarial efficacy in L. sigmodontis and B. malayi infected animals. O ral doses of 5 x 100 mg/kg on consecutive days caused only a temporary decr ease of microfilariaemia levels. By contrast, Bay 44-4400 was highly effect ive against microfilariae of all three species in single oral, subcutaneous and cutaneously applied (spot on) doses. Minimum effective doses (MED, red ucing parasitaemia density by greater than or equal to 95%) determined 3 an d 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 reduction s of microfilaraemia levels by greater than or equal to 95% until day 56. A dulticidal effects, determined as minimum curative doses (MCD, eliminating adult parasites within 56 days by >95%) after single dose treatment were li mited to A. viteae (MCD, 100 mg/kg independent of the route of administrati on). Repeated oral treatment (100 mg/kg on 5 consecutive days) killed all a dult L. sigmodontis but did not affect B. malayi. However, single doses of 6.25 and 25 mg/kg resulted in severe pathological alterations of intrauteri ne 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 Pa rasitology Inc. Published by Elsevier Science Ltd. All rights reserved.