Antifilarial activity of CGP 20,376 in chimpanzees (Pan t. troglodytes) naturally infected with Dipetalonema vanhoofi.
CGP 20,376, a benzthiazole and new antifilarial agent, was investigated at CIRMF in eight wild born chimpanzees naturally infected with Dipetalonema vanhoofi. Single oral doses (3.75, 7.5, 11 and 15 mg/kg) were administered. Drug levels during the first hour after administration were assessed in seven chimpanzees at 10 minute intervals in the blood. Levels of unchanged drug (CGP 20,376) were higher than those of its metabolite (CGP 20,308). However, there was considerable variation between individuals, although the results for each animal were consistent. Because of investigational limitations a complete drug profile could not be established. Unsheathed microfilariae of D. vanhoofi were monitored during the first hour following drug administration in seven chimpanzees. In five the microfilaraemia dropped to low counts within 10 minutes and remained below the initial values for the next 50 minutes while in two other chimpanzees it showed a more irregular reduction. Periodic microfilarial counts over the next 20 months, at roughly 30 day intervals, showed that three chimpanzees, treated with 7.5, 11 and 15 mg/kg respectively, remained free of circulating microfilariae from Day 1 to Day 600, the chimpanzee treated with 3.75 mg/kg remained microfilaremic and, in three chimpanzees low numbers of microfilariae reappeared within one year, whereas in the remaining ape they reappeared after one year. No major clinical adverse effects were observed, but liver function tests showed mild reversible changes at the 11 and 15 mg/kg doses. CGP 20,376 was therefore microfilaricidal, except for the lowest dose, and it was possibly macrofilaricidal in those chimpanzees which remained free of microfilariae for 600 days. Clinically CGP 20,376 was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
Moysan
F
F
Centre International de Recherches Médicales Franceville (CIRMF), Franceville, Gabon.
van Hoegaerden
M
M
Cooper
R W
RW
Bhatia
S C
SC
Poltera
A A
AA
Striebel
H P
HP
Ivanoff
B
B
D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D004153:Dipetalonema / Q000187:drug effects / Q000254:growth & development; D004154:Dipetalonema Infections / Q000188:drug therapy*; D005260:Female; D005368:Filariasis / Q000188:drug therapy*; D005369:Filaricides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008842:Microfilariae / Q000187:drug effects / Q000254:growth & development; D002679:Pan troglodytes; D013844:Thiazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000871:Anthelmintics; D005369:Filaricides; D013844:Thiazoles; C051745:CGP 20376