Absorption kinetics of a series of local anesthetics from rat subcutaneous tissue. I

The subcutaneous absorption kinetics of a homologous series of local anesthetics and lidocaine were studied under controlled pH conditions using a previously described in vivorat model. All local anesthetics exhibited biexponential absorption profiles suggesting accumulation into a tissue compartment. Evidence supporting this hypothesis was supplied by back-extraction of lidocaine from subcutaneous tissue into an acidic environment, by multiple dosing experiments, and by movement of compound into subcutaneous tissue of a postmortem rat preparation. A series of interanimal relationships were demonstrated between structure and parameters of a twocompartment open model. Particularly striking were the correlations between in vivopartition and tissue clearance and the octanolwater (pH 7.95)partition coefficients.Supported by National Institutes of Health Training Grant No. 5T01 GM 00728 from the National Institute of General Medical Sciences and by research funds from the Academic Senate Committee on Research, University of California at San Francisco.Abstracted in part from a thesis submitted by René H. Levy to the Graduate Division, University of California at San Francisco, in partial fulfillment of the Doctor of Philosophy degree requirements.This paper was submitted to a Consulting Editor who served as the Journal Editor during its review process.