Utility of Clinical Chemical Determinations of Drug Concentrations in Biological Fluids

Abstract

Abstract Iatrogenic drug toxicity has become a major medical problem. An approach to avoiding adverse reactions arising from drug accumulation is suggested and explored in depth. Large differences in the rates at which individuals metabolize several commonly used drugs are reviewed, because they illustrate the dangers of prescribing drugs solely according to body weight or surface area, and they emphasize the need for more satisfactory guidelines. Direct measurement of certain drugs in blood is suggested as a convenient, economical, and reliable solution to this problem. In healthy nonmedicated subjects, rates of decay of certain drugs are highly reproducible. In spite of large, genetically controlled differences among subjects in rates of drug metabolism, individuals do not vary significantly with respect to the pharmacological effects produced by certain well-defined blood concentrations of most drugs. For this reason, blood concentrations of most drugs may be conveniently divided into three separate ranges: the low range of therapeutic ineffectiveness; the intermediate range, in which the pharmacologic activity of the drug with negligible toxic side reactions is produced; and, finally, the toxic range. Because many potent drugs with a narrow therapeutic index are in use today—both alone and in combination—it is extremely difficult for the physician to maintain his patients consistently within the therapeutic range and outside of the ineffective or toxic range. Toxicity could be appreciably decreased if this approach of measuring drug concentrations in blood were more widely used in selecting and modifying drug dosage. Clinical advantages and limitations of measuring drug concentrations in blood, as well as the pharmacologic and genetic principles underlying them, are discussed.