Clinical Trials with Bephenium Hydroxynaphthoate Against Hookworm in Ceylon

Abstract

showed that members of a series of new quaternary ammonium compounds were active against a broad range of parasitic nematodes in laboratory and domestic animals. One of the most active compounds, bephenium embonate (benzyldimethyl-2-phenoxyethylammonium embonate), was shown by Rawes and Scarnell (1958) to be of value in the treatment of nematodiriasis in lambs. O)O.(CH1)2.N(CH3)2.CH2 0 mbonate The demonstration of high activity of bephenium salts against Ancylostoma caninum in dogs and cats (Copp et al., 1958) led naturally to preliminary trials in London against hookworm infections in man. We are indebted to Professor A. W. Woodruff, of the Tropical Diseases Hospital, and Drs. D. H. Garrett and M. J. Andrewes, of the Dreadnought Hospital, for carrying out these trials. The results were encouraging and justified more extensive trials against heavier hookworm infections in Ceylon. Tests in laboratory animals, including monkeys, showed that the toxicity of salts of bephenium was low. The less soluble salts, such as the 2-hydroxy-3naphthoate and embonate, were poorly absorbed when given by mouth to human volunteers (Rogers, 1958). Materials and Methods Experiments with A. caninum in dogs and cats (Burrows, 1958), Nippostrongylus muris in rats, and Nematospiroides dubius in mice (Copp and Standen, 1958, in preparation)

Antiparasite Chemotherapy

“…Bephenium hydroxynaphthoate (benzyldimethyl-2-phenoxethyl-ammo nium hydroxynaphthoate) is a crystalline quaternary ammonium antihel minthic. Since the fi rst clinical trial by Goodwin et al (80) documentation regarding this drug is now so extensive that a complete review is beyond the scope of this contribution. The main application of bephenium is for the treatment of hookworm.…”

“…There is however a disparity in its effect upon A. duodenale as compared to that on N. americanus. A single 5 gm dose in adults can be expected to give a cure rate of 80% to 90% for the former infection but only about a 45% rate against the latter (80)(81)(82)(83)(84)(85)(86). Bephenium is also active against A. lumbricoides, giving a cure rate of approximately 65%.…”

The actions and uses of anthelmintics

“…19 A group of quaternary ammonium compounds have recently been shown to have activity against a wide range of nematodes in laboratory and domestic animals and man. 20 OH <: ;' O(CH.).N(CH.),. CII,<:;,…”

“…It is given at a rate of 10 to 20 mg. per kilogram of body weight for 8 to 20 of little value against S. japonicum. Side effects consist of nausea, vomiting, yellow disooloration of the skin, vertigo, restlessness, headache, mental confusion, and tremor.…”

For Hookworm Diagnosis, Is Finding an Egg Enough?

“…Before-and-after treatment data for a given individual should have such a basis. If the determination of the effects of treatment is made on a group, single before-and-after counts furnish a useful average result for the group, even though single counts cannot be relied upon to define the result on any individual within the group (Schapiro and Stoll, 1927;Goodwin et al, 1958;de Azevedo et al, 1959).…”