Comparative table between Pharmacokinetics and Toxicokinetics

Category General aspects Pharmacokinetics Studies drug deposition and activity throughout preclinical and clinical drug development.

Toxicokinetics Toxicokinetics is a unique expansion of the science of pharmacokinetics Recent origin, still in debate

Technical Differences
General Solubility Studies require low doses Less common to see problems of solubility due to dose administration

High doses are needed for studies High doses in toxicokinetics allow drug precipitation in biological fluids of the gastrointestinal tract, with secondary effects not related with the intrinsic effect of the drug Drugs may be administrated with feed, something labor intensive and expensive, which may cause drug storage over large periods and drug degradation problems High doses required for studies usually induce some changes in absorption First-Pass systemic clearance saturates with toxicological doses Allowing changes in drug and metabolite systemic availability Considerable changes due to doses may result in drug penetration into

Stability

Low concentrations and amounts of the drugs tested usually avoid stability problems

Absorption

First-Pass Effect or Presystemic Clearance

Protein binding

Drugs commonly absorbed by passive processes, with little influence of the quantity of drug administrated in the intrinsic adsorption The bio-availability is different for both cases, in pharmacokinetics due to relatively low doses required, problems of toxicologic hepatic sequelae are less common Binding of compounds to plasma proteins and other tissue is generally

Metabolism Renal excretion Physiological Feedback

Drug interaction

reversible and always different tissues as saturable nervous system Metabolism varies considerably in both cases because of the doses, this is a result of the metabolism being a substrate concentration dependent process In both cases the renal excretion is more influenced by the circulating drug concentration, and can be a saturable and nonsaturable mechanism The effect could be toxic High concentration of or not, that depends on drugs causes toxic effects the nature of the to the host, by definition administrated drug and the dose In both cases depending on the site and the nature of the toxic event, could result in absorption, distribution, metabolism and excretion changes Drug interaction could be affected by the concentration, so there could be important differences in the drug behavior depending on the applied dose. Studies are carried out in animals and human beings depending on the Phase of the trials. Both Preclinical and Clinical trials offer important information to define the activity and safety of the drug for human use. These are not only useful, but very important Facilitated by means of well-established end points Studies are carried out exclusively in animals The objective of the trials is to establish appropriate drug exposure in certain species; as well as the metabolic profiles of new chemicals. This helps to predict toxicity and tolerance in humans based on preclinical information Extremely difficult because of the very poor and frequently unpredictable and points in experimental animals. Complicated because of the capricious interspecies differences in organ and tissue sensitivity within animal species, and between animal species and

Philosophical Differences
Trials

Studies

humans.

References
Welling, Peter G. (1995). Differences Between Pharmacokinetics and Toxicokinetics Toxicol Pathol 23: 143