THE FATE OF PHENOTHIAZINE IN THE GASTROINTESTINAL TRACT OF THE SHEEP

Abstract

The methods for estimating phenothiazine and phenothiazone in biological materials have been investigated. It has been shown that when phenothiazine, or phenothiazone is treated with bromine (under the conditions described), a red color is produced which has absorption maxima at the following wavelengths: 240, 282, 291, 375, and 510 mμ. Phenothiazone, in 95% ethanol, has a spectrum with absorption maxima at 237, 273, 280, 288, 369, and 508 mμ. Thus the bromine method is not applicable for distinguishing between these two compounds. It is shown also that phenothiazine may interfere with the estimation of phenothiazone when the latter is measured by the light absorption of its free radical. The ultraviolet absorption spectra of phenothiazine and diphenylamine o-sulphoxide have been determined. The spectrum of the former compound has a maximum at 254 mμ (with a small maximum at 318 mμ), and that of the latter has maxima at 227, 272, 302, and 335 mμ. Leucophenothiazone also has a maximum at 254 mμ.While excretion studies on sheep confirm that 40% of the orally administered phenothiazine is lost in the urine, it is shown that the absorption of the drug from the intestine is not dependent upon oxidation to phenothiazone in the rumen. Indeed, the drug appears to be unchanged in this organ. In a postmortem examination of the gastrointestinal tract no phenothiazone was found proximal to the bile duct. It is suggested that phenothiazine is absorbed from the rumen unoxidized. In support of this it is confirmed that some phenothiazine may be recovered unchanged from the urine of the sheep.