Studies on the absorption of practically water-insoluble drugs following injection V: Subcutaneous absorption in rats from solutions in water immiscible oils.

To elucidate the kinetics and mechanisms of subcutaneous absorption of practically water-insoluble drugs in oily solutions, the absorption behaviors of select azo dyes and other prototype agents were investigated by a local clearance method in the dorsum in intact rats. The absorption of the drug components appeared to be first-order. The first-order rate constant (k) was inversely proportional to the cube root of the injection volume. In more limited studies, essentially the same behavior was observed in the rat abdomen, and the difference in k between the dorsal and abdominal injections was slight. The comparison of k of a given compound from different oily vehicles showed that k was governed predominantly by the distribution coefficient (K) between the oily vehicle and the aqueous subcutaneous medium and depended little on the viscosity of the vehicle. This distributioning relationship was shown through correlation of the rate constants with in vitro distribution coefficients. A plot of log k versus log K for all the compounds tested was linear with a slope of approximately -0.7. This linear relationship allows adequate prediction of absorption rates of other drugs from oily vehicles. The observed subcutaneous absorption rates and behaviors are compared with previous results involving the intramuscular route.