EXHIBIT G Kinetics A Speedy Review

Kinetics is the study of the speed of a chemical reaction or process and is a critical element in toxicology. Most processes described in the discipline follow zero- and first-order kinetics. Recall that rate laws are employed to determine concentrations as a function of time. Although there are other variables and factors, the elimination of a xenobiotic substance from the body is fundamentally dependent on the kinetics of the reactions involved. Elimination processes often involve catalysts (enzymes), the role of which is central in determining the overall speed of the elimination, since a catalyst reduces the energy of activation. Eg. 

Concepts of mechanism and rate-limiting steps apply as well, as can be illustrated with a simplified view of the metabolic processing of ethanol  

Net C2H5OH---------- C2H3O2, rate-limiting step = first 

Note this is the same equation used to derive the first-order-rate half-life described in equations 6-2 through 6-5. The rate constant is specified as the elimination rate constant lq,. The first-order rate law can be restated as follows to allow the calculation of concentration as a function of time  

If not given, the rate constant can be derived from the half-life and equation 6-5. A single-compartment model is based on the assumption that an injected drug is instantaneously distributed in the plasma and tissues. Such a model is a good starting point and applicable in many situations. 

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