Investigations on the antibilharzial action of miracil D (nilodin)

The history of attempts to develop a drug for the oral treatment of bilharzia disease in human beings is briefly reviewed, concluding with an account of the development of the new antibilharzial drug miracil D (nilodin). A description is given of tests in which animals experimentally infected with B. mansoni and B. haematobia were treated with solutions of miracil D administered by the oral route. In those animals to which a sufficient dosage was given over a sufficient length of time, for example, five doses of 40 to 50 mg. per kg., both viable ova and the symptoms of the disease disappeared and at autopsy only dead and disintegrating worms were found. However, in lower dosages the drug appeared to be erratic in its action, killing some of the worms and curing some animals when used in a given dosagw while failing to kill others. An account is also given of clinical trials in which miracil D was administered to human patients suffering from both varieties of bilharzia disease. Here, also, in lower dosages the drug appeared to be erratic in its action, curing some patients and failing to cure others; but the results of the later trials, in which higher and more frequent doses were given, were more consistent and improvement was more marked. In the earlier series of trials, doses of 400 mg. were administered twice or thrice at 3-day intervals. In the later series of trials, doses of up to 300 mg. at 12-hourly intervals were given for as long as a fortnight. Viable ova disappeared from the urine or faeces, haematuria vanished and the physical condition of the patient substantially improved, but most cases later showed partial relapse. It is impossible to generalize too widely with regard to dosage since this varied according to the weight, physical condition and urea clearance rate of the patient. Further improvement was achieved after second treatment, and although few complete cures were obtained the reduction in the number of ova and the amount of blood in urine or faeces was considerable. The most satisfactory clinical results were achieved by keeping the blood miracil D, as we believe, up to the lethal level for the parasites by administration every 12 hours. The minimum effective dosage seemed to be 5 mg. per kg. every 12 hours for a minimum period of 5 days although a higher rate is almost certainly desirable. The pharmacology of miracil D is briefly reviewed and the toxic symptoms observed during administration to human patients are recorded. Such toxic symptoms are generally slight and appear only to affect one out of five or six patients. These toxic symptoms include anorexia or even vomiting, abdominal pain, and, sometimes, giddiness and noises in the ear. Whether or not these toxic symptoms are associated with some undetermined contra-indication or whether they are due to insufficient kidney function leading to undue accumulation of the drug in the body and an exceptionally high blood level has not yet been discovered. Contra-indications have yet to be determined but not obvious ones have been observed, although it is probable that administration of miracil D would prove to be incompatible with heart disease or organic disease of the kidneys.