Drug distribution kinetics

DIFFUSION OF LIGAND TO RECEPTOR Drug clearance, dosage, PHARMACOKINETICS Drug distribution kinetics, PHARMACOKINETICS Drug excretion rates,... 

Herman, R. A. and P. Veng-Pedersen. 1994. Quantitative structure-pharmacokinetic relationships for systemic drug distribution kinetics not con ned to a congeneric sefi harm. Sci83 423-428. 

The impact of physiological changes on drug distribution kinetics has not been studied extensively. For example, it is known that pregnancy alters the elimination kinetics of many drugs. But physiological... 

Drug Distribution. After administration, a drug may be distributed either generally or selectively in the body. The distribution pattern depends on many factors, including the pattern and time-course of blood (low, diffusion of drugs into tissues, binding of drugs to plasma proteins and cellular compartments, and elimination kinetics and mechanisms. 

Compartmental models of PK analysis are widely used to describe drug distribution and disposition. In these models, the body is assumed to be composed of one compartment or more and the drug kinetics can be defined by differential equations... 

Factors analogous to those affecting gut absorption also can affect drug distribution and excretion. Any transporters or metabolizing enzymes can be taxed to capacity—which clearly would make the kinetic process nonlinear (see Linear versus Nonlinear Pharmacokinetics ). In order to have linear pharmacokinetics, all components (distribution, metabolism, filtration, active secretion, and active reabsorption) must be reasonably approximated by first-order kinetics for the valid design of controlled release delivery systems. 

Among various initial concentration distributions in a matrix, the sigmoidal drug distribution or a staircase distribution resembling a sigmoidal pattern furnishes zero-order release kinetics for the planar geometry. There are various methods to build concentration gradient matrix systems. The most convenient way to achieve the... 

This section proposes the use of a semi-Markov model with Erlang- and phase-type retention-time distributions as a generic model for the kinetics of systems with inhomogeneous, poorly stirred compartments. These distributions are justified heuristically on the basis of their shape characteristics. The overall objective is to find nonexponential retention-time distributions that adequately describe the flow within a compartment (or pool). These distributions are then combined into a more mechanistic (or physiologically based) model that describes the pattern of drug distribution between compartments. The new semi-Markov model provides a generalized compartmental analysis that can be applied to compartments that are not well stirred. 

A full description of drug distribution can be complex, whether it is based on a knowledge of tissue perfusion and partition of drug from plasma to tissue, or whether it is based on a kinetic analysis of plasma concentration-time curves. One of the major descriptive parameters, which is probably of most interest to the toxicologist, is the volume of distribution (F ). This is the amount of drug in the body A) divided by the plasma concentration (c) after distribution equilibrium has been established. 

In the disposition model shown in Figure 4.9, the kinetics of drug distribution and elimination are represented by a single compartment with first-order elimination as described by the equation... 

The paucity of reliable bioavailability data in patients with impaired renal function underscores the cumbersome nature of most absolute bioavailability studies in which oral and intravenous drug doses are administered on two separate occasions. The validity of this approach rests on the assumption that the kinetics of drug distribution and elimination remain... 

One can now appreciate why conventional definitions of pharmacokinetics are a little different from the definition given here. The conventional definitions make references to events other than temporal and spatial distribution. These events are, in fact, consequences of a drug s kinetics, and thus the two should be separated. The processes of drug absorption, distribution, metabolism, and elimination relate to parameters that can only be estimated from a mathematical model describing the kinetics of the drug. The point is that, to understand the mathematical basis of pharmacokinetic parameter estimation, it is necessary to keep in mind the separation between kinetics per se and the use of data to estimate pharmacokinetic parameters. 

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