Toxicokinetics vs. Pharmacokinetics

Pharmacokinetics (PK) is the determination of the extent of Absorption, Distribution, Metabolism, and Excretion (ADME) of a small molecule compound, peptides, and biologics/large molecules. Toxicokinetic (TK) analysis provides bioanalytical support for nonclinical safety and toxicology studies in animals. The goal of TK is to correlate findings of toxicity with a corresponding level of drug exposure.TK is defined as the generation of PK data, either as an integral component in the conduct of nonclinical toxicity studies or in specifically designed supportive studies to assess systemic exposure.

Principles of TK and PK

• PK 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. Mathematical models and equations are used to describe and predict these phenomena. Pharmacodynamics is the term used to describe an investigation of the relationship of xenobiotic concentration to clinical effects.
• TK, which is analogous to PK, is the study of the absorption, distribution, metabolism, and excretion of a xenobiotic under circumstances that produce toxicity. TK, which is analogous to pharmacodynamics, is the study of the relationship of toxic concentrations of xenobiotics to clinical effects.

Differences Between TK and PK

TK is a unique expansion of the science of PK. The major difference between the 2 disciplines, of course, is that TK studies are generally carried out at much higher doses than those used in PK studies. In toxicology, the ability of the body to cope with a drug is extended to the absolute limit, indeed, to the point of toxicity.

Technical differences between TK and PK

Different dose levels used in TK, compared to PK, give rise to technological changes in such factors as solubility, stability, absorption, pre-systemic clearance, protein binding, and metabolism that may be influenced by dose size, and may give rise to profound differences in the design and interpretation of studies. Pharmacokinetic and toxicokinetic studies also have different objectives.

Philosophical differences between TK and PK

• The major difference between PK and TK lies in their overall objectives. The primary goal of TK is to correlate findings of toxicity (not therapeutic efficacy) with a corresponding level of exposure to an experimental drug compound.
• Whereas pharmacokinetic-pharmacodynamic studies are often facilitated by means of well-established endpoints, toxicokinetic-toxicodynamic studies are extremely difficult because of the very poor and frequently unpredictable endpoints in experimental animals.
• The TK arm of a nonclinical toxicology study generally has fewer time points, fewer subjects, and fewer endpoints compared to nonclinical and clinical PK studies.

Creative Bioarray Relevant Recommendations

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