Phase 1 tolerability and searching dose studies with 4-isothiocyanato-4'-nitrodiphenylamine (C.9333-Go/CGP 4540), a new anthelmintic

Br J Clin Pharmacol. 1977 Aug;4(4):463-7. doi: 10.1111/j.1365-2125.1977.tb00763.x.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aniline Compounds / adverse effects*
  • Anthelmintics / administration & dosage
  • Anthelmintics / adverse effects*
  • Anthelmintics / therapeutic use
  • Diphenylamine / administration & dosage
  • Diphenylamine / adverse effects*
  • Diphenylamine / analogs & derivatives
  • Diphenylamine / therapeutic use
  • Drug Evaluation
  • Feces / parasitology
  • Female
  • Hookworm Infections / drug therapy
  • Hookworm Infections / parasitology
  • Humans
  • Isothiocyanates
  • Male
  • Middle Aged
  • Parasite Egg Count
  • Thiocyanates / administration & dosage
  • Thiocyanates / adverse effects*
  • Thiocyanates / therapeutic use
  • Time Factors

Substances

  • Aniline Compounds
  • Anthelmintics
  • Isothiocyanates
  • Thiocyanates
  • Diphenylamine
  • amoscanate