Abstract

1. A method is described for the estimation of phenylbutazone in biological fluids and tissues.

2. Phenylbutazone is rapidly and completely absorbed from the gastrointestinal tract of man. Intramuscular absorption, on the other hand, is relatively slow, because of localization of the drug at the site of the injection.

3. Phenylbutazone at therapeutic concentrations is highly bound to plasma proteins. About one-third of a single dose of the drug is localized in plasma.

4. The drug is almost completely metabolized in the body. After discontinuance of dosage, the rate of biotransformation in man is slow, averaging about 20 per cent per day, but varies considerably in different subjects. Subjects with Laennec's cirrhosis of the liver metabolize the drug as readily as normal subjects.

5. Plasma levels of phenylbutazone are not proportional to dosage. Plasma levels achieved on doses of 1600 mgm. per day are only a few per cent higher than those obtained on doses of 800 mgm. per day. On both dosage regimens, absorption is complete and urinary excretion of the drug is negligible.

6. Different species vary markedly in the rates at which they metabolize phenylbutazone. The biologic half-life of the drug is about 72 hours in man, 6 hours in dog and rat, 5 hours in guinea pig, and 3 hours in rabbit.