Physiological disposition of some semisynthetic penicillins.

Abstract

Two phenoxy penicillins and one phenylthio penicillin were selected for a study of physiological disposition. Phenylthiodiphenyl penicillin was, however, rejected because it underwent complete biotransformation. The resultant substance retained antibacterial activity but lost its resistance to the enzyme β-lactamase.The rate of absorption of phenoxymethyl and phenoxybenzyl penicillins from rat small intestine was at variance with the properties of the substances and the concept of passive, nonionic diffusion. A more detailed study excluded the possibility that some form of specialized transport was involved. The data are consistent with a delay in absorption caused by an interaction between penicillin and some component of intestinal epithelium. Absorption may be further hindered by the formation of penicillin micelles. The relatively polar nature of such micelles would tend to reduce the ability of the parent substance to penetrate lipid-like membranes.Maintenance of high concentrations in the blood is favored by a numerically large partition coefficient, and the associated high degree of binding to albumin and decrease in acidity. It appears that differences in both biliary and renal tubular secretion also play an important part.