BIOCHEMICAL ASPECTS OF THE TOXICITY OF ATABRINE

II. THE INFLUENCE OF THE DIET UPON THE EFFECTS PRODUCED BY REPEATED DOSES OF THE DRUG

¹ From the Merck Institute for Therapeutic Research, Rahway, N. J.

Rats maintained on a high protein-low fat diet appear to resist toxic effects upon the liver of the daily administration of atabrine to a greater degree than rats maintained on low-protein diets or a diet high in both protein and fat. Inhibition of liver function in the rat was not detected by the bromsulfalein test, the determination of the icteric index, bilirubin or prothrombin time. Plasma fibrinogen values appear to parallel the toxic effects of atabrine upon the liver.

Daily administration of large doses of atabrine (25 to 50 mgm. per kgm.) to dogs produces an inanition within 3 to 6 weeks. At lower dose levels (5 to 10 mgm. per kgm.) this is not evident three to five months after initiation of drug administration.

Plasma fibrinogen levels are more rapidly increased by the daily administration of atabrine in protein depleted dogs than in dogs maintained on a stock ration. This effect of the drug is reversed by restoring protein to the diet of the depleted dogs.

Determinations of the prothrombin time, icteric index, bilirubin, urinary urobilin, urea, non-protein nitrogen, urinary protein, and the Hanger flocculation time afforded no evidence of depressed function in these dogs.