Pharmacodynamic and pharmacokinetic measurements in cardiovascular‐renal drugs

Methodologic advances in drug assay techniques and their growing availability provide a potentially powerful tool in the optimal use of important GV‐renal drugs. Blood level data have provided the bases for describing the kinetic behavior in the body of a number of agents, and this information in turn has allowed the construction and assessment of dose regimens under varying conditions. For substances with a narrow margin of safety like the cardiac glycosides and for those often used prophylactically like the antiarrhythmics, such pharmacokinetic profiles have been shown to be clinically useful. However, correct interpretation of a drug's blood levels must take into account the factors responsible for the kinetic pattern observed since these may differ as after a single dose and during a steady‐state equilibrium. In addition, the processes of drug absorption, distribution, and bioelimination that influence a compound's pharmacodynamics are themselves subject to normal variability as well as to alteration by pharmaceutical preparation, other drugs, disease states, etc. Appreciation of these modifying effects is crucial in the appropriate application of a drug's general kinetic parameters to specific clinical situations. Besides their role in defining kinetic and dynamic activity, measurements of drug concentrations in the blood may help in the evaluation of inappropriate drug responses as when “standard” dose regimens fail to produce the expected results or lead to unanticipated toxicity. Yet even the usually close correlation between blood level and pharmacologic effect upon which this use is predicated varies normally among individuals and may be changed significantly by various pharmacologic and pathologic factors.