Phase 1 tolerability and searching dose studies with 4-isothiocyanato-4'-nitrodiphenylamine (C.9333-Go/CGP 4540), a new anthelmintic.
1 Phase 1 and 2 studies were carried out in thirteen volunteers and thirty patients with hookworm anaemia with a new anthelmintic, 4-isothiocyanato-4'-nitrodiphenylamine (C.9333-Go/CGP 4540). Single and multiple doses were administered by mouth under careful supervision by the staff of the clinical pharmacology unit. 2 4-Isothiocyanato-4'-nitrodiphenylamine (C.9333-Go/CGP 4540) was well tolerated in volunteers up to a single dose of 1750 mg and in patients up to 3000 mg in divided doses. Side effects were rare, transient and mild. One patient had moderate giddiness for 24 h after the compound. The laboratory investigations did not show any adverse effects on organ functions. Transient non-specific changes in the T-wave were occasionally observed in the e.c.g. 3 Multiple doses (125 mg, 250 mg or 1000 mg X 3) of the compound were highly effective in eradicating hookworm infection, as judged by almost 100% reduction in faecal egg counts and significant recovery of parasites from 24 h stool samples. The compound also showed activity against A. lumbricoides, T. trichiura and E. vermicularis. The compound appears to be promising and more studies, in a field situation, are desirable.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000814:Aniline Compounds / Q000009:adverse effects*; D000871:Anthelmintics / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004159:Diphenylamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000627:therapeutic use; D004341:Drug Evaluation; D005243:Feces / Q000469:parasitology; D005260:Female; D006725:Hookworm Infections / Q000188:drug therapy / Q000469:parasitology; D006801:Humans; D017879:Isothiocyanates; D008297:Male; D008875:Middle Aged; D010270:Parasite Egg Count; D013861:Thiocyanates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
D000814:Aniline Compounds; D000871:Anthelmintics; D017879:Isothiocyanates; D013861:Thiocyanates; D004159:Diphenylamine; C012391:amoscanate