An Overview of Kinetics

The fate of a drug in the body is related to the efficacy of clearing organs and to the fact that most of its interactions in the body (effects, storage, and metabolism) involve reversible binding to specific proteins, receptors, acceptors, and enzymes. Covalent bonds may sometimes be involved, which prolong effects or cause toxicity.

The fate of a drug in the body depends on a series of transfers through and between membranes and into, out of, or between cells during which it may be transformed. Kinetics of transfer and transformation result from either passive or active processes. Passive transfers are described according to Fick's law:

where dM/dt is the amount of drug transferred during time dt, DC is the gradient of concentration, MWis the molecular weight of the transferred solute, and kf is a constant related to its lipophilicity (solubility in membranes) and hydrophilicity (solubility in water). As a general rule, drugs transferred by this process have a MW below 500. S is the surface available for transfer and d is the thickness of this surface or membrane.

This equation is valid for linear kinetics where rate and concentration are directly related. The membrane transfer depends also on other parameters (see 5.12 Biological In Vitro Models for Absorption by Nonoral Routes; 5.13 In Vitro Models for Examining and Predicting Brain Uptake of Drugs; 5.19 Artificial Membrane Technologies to Assess Transfer and Permeation of Drugs in Drug Discovery; 5.28 In Silico Models to Predict Oral Absorption; 5.29 In Silico Prediction of Oral Bioavailability; 5.30 In Silico Models to Predict Passage through the Skin and Other Barriers; 5.37 Physiologically-Based Models to Predict Human Pharmacokinetic Parameters; 5.42 The Biopharmaceutics Classification System).

Active transfers are energy consuming as defined in Michaelis kinetics by the general equation:

where dM/dt is the amount of drug transferred or metabolized during time dt, C is the drug concentration, Vmax is the maximum rate of kinetics, and Km is the Michaelis constant. Since drug concentrations are generally very low, C is often negligible compared to Km and the equation becomes:

This approximation yields linear kinetics.

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