1963 年 83 巻 9 号 p. 871-874
A quantitative examination was made on tetracycline (I) epimerization in the digestive tract and its influence on absorption. I undergoes a reversible epimerization at 4-carbon to form 4-epi-tetracycline (II). The epimerization occurs in the pH range of ca. 3-6 and its rate is increased by the presence of certain anions, such as a citrate, phosphate, or acetate. Other adjuvants usually incorporated in preparations of I, such as glucosamine hydrochloride, have very little effect on the epimerization rate whereas calcium ion markedly decreases it. Oral administration of I with or without citric acid or of II indicated that no detectable amount of II is excreted in the urine from a rat or humans although the intestinal content from the rat clearly demonstrated the presence of II. Absorption experiments from the rat stomach and small intestine were carried out using pre-equilibrated solutions of pH 4, 5, and 6. The result indicates that little absorption of I and II occurs from the stomach and that I is more rapidly absorbed than II from the small intestine. For example, the degrees of 90-minute absorption of I and II at pH 5 are 13% and 0.2%, respectively. Considering all the evidences presented here, it is concluded that epimerization in the digestive tract is one of the reasons to be accounted for the relatively low recovery of I in the urine.