Pharmacokinetics is the study of the absorption, distribution, metabolism, and excretion of xenobiotics. Xenobiotics are substances that are foreign to the body and include natural or synthetic chemicals, drugs, pesticides, environmental agents, and industrial agents.56 Mathematical models and equations are used to describe and to predict these phenomena. Pharmacodynamics is the term used to describe an investigation of the relationship of therapeutic xenobiotic concentration to its clinical effects. Toxicokinetics, which is analogous to pharmacokinetics, is the study of the absorption, distribution, metabolism, and excretion of a xenobiotic under circumstances that produce toxicity. Toxicodynamics, which is analogous to pharmacodynamics, is the study of the relationship of toxic xenobiotic concentrations to their clinical effects.
Overdoses challenge the mathematical precision of toxicokinetics and toxicodynamics because many of the variables, such as dose host variables, time of ingestion, and presence of vomiting, or diarrhea, that affect the result are often unknown. In contrast to the therapeutic setting, atypical solubility characteristics are noted, and saturation of enzymatic processes occurs. Intestinal or hepatic enzymatic saturation or alterations in transporters enhance absorption through a decrease in first-pass effect defined as metabolism before the xenobiotic reaches the systemic circulation.5,85 Saturation of plasma protein binding results in the availability of more unbound xenobiotic in the plasma. Saturation of hepatic enzymes or saturation of active renal tubular secretion leads to prolonged elimination (metabolism and excretion). In addition, age, obesity, gender, pharmacogenetics and pharmacogenomics, chronopharmacokinetics (diurnal variations), and the effects of illness and impairment of hepatic and renal function, as well as cardiac output and splanchnic perfusion all further limit the ability to achieve precise analyses.6,22,47,52,75,81 Furthermore, various treatments may alter one or more pharmacokinetic and toxicokinetic parameters. There are numerous approaches to recognizing these variables, such as obtaining historical information from the patient’s family and friends, performing pill counts, procuring sequential serum concentrations during the phases of toxicity, and occasionally repeating a pharmacokinetic evaluation of that same xenobiotic during therapeutic dosing to obtain comparative data.
Although different, plasma concentration and serum concentration are terms often used interchangeably. When a reference or calculation is made with regard to a concentration in the body, it is actually a plasma concentration. When concentrations are measured in the laboratory, a serum concentration (clotted and centrifuged blood) is often determined. In reality, the laboratory measurements of most xenobiotics in serum or plasma are nearly equivalent. Frequently, this is not the case for whole-blood determination if the xenobiotic distributes into the erythrocyte, such as lead and most other heavy metals.
Despite all of the confounding and individual variability, toxicokinetic principles are nonetheless applied to facilitate our understanding and to make predictions. These principles are used to help evaluate whether a certain antidote or extracorporeal removal method is appropriate for use, when the serum concentration might be expected to decrease into the ...