The Pharmacokinetization of Psychiatry

The titration and monitoring of drug therapy using pharmacokinetic principles along with measurements of serum or plasma drug concentrations have become essential components of pharmacotherapy in many areas of clinical medicine, including the treatment of asthma, seizure disorders, certain infectious diseases, and cardiac arrhythmias. The value of pharmacokinetic principles in these therapeutic areas follows from several mathematical and biologic requisites. The first is that the drug's steady‐state serum or plasma concentration (Css) during multiple dosage bears a reasonably predictable relationship to clinical outcome. When Css falls in some “therapeutic range,” the likelihood of clinically effective drug therapy is maximized. If Css exceeds this range, toxicity becomes increasingly likely, while values of Css below the therapeutic range may be therapeutically ineffective. Second, Css can be expressed as the quotient of two independent factors: dosing rate divided by total clearance. The health care professional has control over dosing rate, and therefore controls one major determinant of Css. All else being equal, Css will rise or fall correspondingly as dosing rate is changed. However, the health care practitioner has no control over total clearance, the other major determinant of Css. Clearance best describes the capacity of a given patient to remove a given drug, and is a unique property of each drug in each individual. Because clinicians seldom know the clearance of a particular drug in a particular patient, clearance usually must be estimated, based on findings from prior pharmacokinetic studies along with consideration of physiologic factors, disease states, or drug interactions that may alter clearance.