Noninvasive chemical methods of estimating pharmacokinetic parameters.

Two noninvasive methods have been advocated for pharmacokinetic and bioavailability studies. The measurement of the salivary and urinary excretion of drugs and their metabolites may avoid sampling blood, particularly in introductory studies. The measurement of the salivary concentrations of drugs is of most value in studies on compounds which are little ionized at physiological pH values. Well studied examples where there is a good parallelism between salivary and plasma drug concentrations include the neutral drug, ethanol, the weakly acidic drugs, phenytoin and sulphapyridine, and the weakly basic drugs, carbamazepine and antipyrine. Data on the salivary secretion of more strongly acidic or basic drugs are often conflicting and further work is required to determine the usefulness of measuring the salivary secretion of such drugs in pharmacokinetic and biopharmaceutical studies. Studies on the rate of excretion or cumulative excretion of drugs and their metabolites in urine may provide good estimates of the terminal half lives of drugs. However, accurate determinations of the kinetic parameters of rapid processes are not obtainable from studies on urinary excretion. Reliable data can only be obtained if the timing of urine collections is precise and if there are no significant losses of urine.