DISTRIBUTION, EXCRETION, AND RATE AND SITE OF DETOXIFICATION OF METRAZOL

¹ From the Department of Pharmacology and Toxicology of the University of Wisconsin, Madison

1. A method for the quantitative determination of metrazol in biological material is described. Recoveries of 89 per cent or better were obtained from rats given varying amounts of the drug. The duplicate analyses of the different tissues analyzed were within 2 mgm. per cent of the mean, the majority of the determinations being within 1 mgm. per cent of the mean. The recovered metrazol was checked by melting point and mixed melting point determinations and found to agree with the accepted value for this drug.

2. The distribution of metrazol in the blood, liver, muscle and brain was determined at hourly intervals and found to be equally distributed in these tissues. No tissues analyzed appeared to have any particular affinity for the drug.

3. The rate of detoxification of metrazol was directly proportional to the concentration of the drug in the tissues.

4. Only traces (less than 3 mgm. per 24-hour specimen) of metrazol were excreted unchanged in the urine of dogs or man following relatively large doses of the drug. No evidence was found which would indicate that metrazol was excreted in a conjugated or easily hydrolyzable form in the urine or feces.

5. The kidney has little or no effect on the detoxification of metrazol, whereas the evidence presented indicates that the liver plays an important part in this detoxification.