Use of the analogue computer to examine the quantitative relation between urinary pH and kidney reabsorption of drugs partially ionized at physiological pH

Abstract

Abstract A method, involving the use of an analogue computer, is described for determining a quantitative relation between measured urinary pH and the kidney tubular reabsorption of certain drugs under normal conditions of fluctuating urinary pH. The method is based on the use of drug excretion versus time profiles under normal conditions and of absorption, metabolism and excretion rate constants, determined under conditions of controlled urinary pH, e.g. constant acidic pH (<5) in the case of basic drugs. In support of the theoretical treatment, experimental results, using amphetamine as a model drug, are presented. The implications of the method are discussed with respect to the evaluation of drug formulations under normal urinary pH conditions.