Shigeo Kachi (1), Mamoru Terada (1) and Hisakuni Hashimoto (2)
(1) Department of Parasitology and (2) Department of Pharmacy, Hamamatsu
University School of Medicine, 3600 Handa-cho, Hamamatsu 431-3192, Japan
Abstract: To enhance the bioavailability of PF1022A (cyclo(D-lactyl-L-N-methylleucyl-D-3-phenyllactyl-L-N-
methylleucyl-D-lactyl-L-N-methylleucyl-D-3-
phenyllactyl-L-N-methylleucyl)), a newly developed antinematode drug, we
examined whether the new drug has polymorphism or not. First, four forms
of PF1022A, designated as form alpha, form I, form II and form III of PF1022A,
were prepared. By examining physicochemical properties of these forms by
various methods including X-ray powder diffractometry and differential scanning
calorimetry, it became apparent that PF1022A had one amorphous (form alpha)
and three crystalline polymorphic forms, form I, form II and form III. Secondly,
a dissolution study was carried out, and form alpha and form III were found
to have higher solubility than form I and form II. Thirdly, anti-larval
effects of the 4 forms of PF1022A on tissue-dwelling nematodes, Angiostrongylus
costaricensis, in mice were compared when given orally for 5 successive
days at 10 or 40 mg/kg/day. Significant effects were observed in almost
all parameters in host mice and worms in the groups treated with form alpha
or form III, each at 40 mg/kg, but form I and form II had little effect.
The present results suggest that PF1022A has polymorphism and that the form
alpha and form III were more effective against tissue-dwelling nematodes
than the form I and form II when given orally.
Keywords: PF1022A, Anthelmintic, Polymorph, Amorphous, Angiostrongylus
costaricensis