title: Filaricidal efficacy of anthelmintically active cyclodepsipeptides.
abstract: PF 1022A, a novel anthelmintically active cyclodepsipeptide, and Bay 44-4400, a semisynthetic derivative of PF 1022A were tested for filaricidal efficacy in Mastomys coucha 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 > or =95%) determined 3 and 7 days after treatment were 3.125-6.25 and 6.25-12.5mg/kg, respectively. Using the spot on formulation, doses of 6.25mg/kg (L. sigmodontis), 12.5mg/kg (A. viteae) and 25mg/kg (B. malayi) were required to cause reductions of microfilaraemia levels by > or =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, 100mg/kg independent of the route of administration). Repeated oral treatment (100mg/kg on 5 consecutive days) killed all adult L. sigmodontis but did not affect B. malayi. However, single doses of 6.25 and 25mg/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.
authors.affiliation: Institute for Parasitology, Justus Liebig University Giessen, Rudolf-Buchheim-Strasse 2, D-35392 Giessen, Germany. horst.zahner@vetmed.uni-giessen.de
authors.forename: H
authors.initials: H
authors.lastname: Zahner
authors.forename: A
authors.initials: A
authors.lastname: Taubert
authors.forename: A
authors.initials: A
authors.lastname: Harder
authors.forename: G
authors.initials: G
authors.lastname: von Samson-Himmelstjerna
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000494:pharmacology*; D017178:Brugia malayi; D047630:Depsipeptides; D004153:Dipetalonema; D005260:Female; D005368:Filariasis / Q000188:drug therapy* / Q000469:parasitology; D005370:Filarioidea; D007279:Injections, Subcutaneous; D009115:Muridae; D018512:Parasitemia / Q000469:parasitology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats
chemical_list: D000871:Anthelmintics; C439266:Bay 44-4400; D047630:Depsipeptides; D010456:Peptides, Cyclic; C075544:PF 1022A