I. G. Schmidt
Apr 1, 1966
Citations
0
Influential Citations
49
Citations
Quality indicators
Journal
Annals of the New York Academy of Sciences
Abstract
Our initial investigation of the therapeutic potentialities of ethambutol as an antituberculosis drug included two distinct studies. One of these was aimed a t delineating the capacity of this agent to modify the development of induced pulmonary tuberculosis in the rhesus monkey; its more important features were dealt with in the preceding report.' The second study was concerned with the capacity of ethambutol to produce toxicological reactions when administered in doses up to and somewhat in excess of those employed in the therapeutic evaluation. This toxicological study involved a group of 12 monkeys, 5 pairs of animals receiving ethambutol in daily doses of 25, 50, 100, 200 or 400 mg./kg. body weight, and one pair of untreated controls. One of those receiving 400 mg./kg. doses succumbed to an intercurrent enteric infection on the 164th treatment day. The responses of the remaining 9 monkeys over a 26-week treatment period were negative. While this initial toxicological study was in progress, evidence began to accumulate which showed that the administration of a mixture of ethambutol and its L-isomer to human patients in doses approximating 100 mg./kg. evoked rather severe visual disturbances.' This finding led to a second experiment in which both ethambutol and the DL mixture were administered to monkeys in doses greater than those employed in the initial study. I t soon became apparent that the DL mixture, administered a t daily doses of 400 to 1200 mg./kg. for relatively short time periods, evoked visual disturbances and other adverse reactions indicative of injury to the central nervous system. More prolonged administration of 800 to 1600 mg./kg. doses of ethambutol produced a similar syndrome. A comparison of the neurotoxic effects of ethambutol and its racemate will be published el~ewhere.~ Histologic study of the brains and cords, eyes and optic nerves of the recipients of these larger doses of ethambutol revealed lesions and neuroanatomical changes which, in the main, seemed sufficient to account for the observed functional disturbances. This report deals with the location and