Kinetics of drug distribution

Thiopental is a very lipophilic drug that readily crosses the blood brain barrier. Very shortly after injection, the concentration in the brain peaks, and for a few minutes the 

However, after a short time, the drug leaves the brain again and accumulates in the lean tissues (such as muscle), from where it finally redistributes to the body fat. This reflects that the fat provides the most favourable (lipophilic) environment however, since it is only weakly perfused, substance exchange works more slowly than with the other tissues. Note that, in this particular case, drug action is not terminated by elimination of the drug (as is usually the case), but solely by its redistribution from the site of action (the brain) to inert reservoirs (muscle / fat). Ultimate elimination is very slow - it takes days to complete - and involves hepatic metabolism of the drug, followed by urinary excretion. 

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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... 

For a drug to interact with a target, it has to be present in sufficient concentration in the fluid medium surrounding the cells with receptors. Pharmacokinetics (PK) is the study of the kinetics of absorption, distribution, metabolism, and excretion (ADME) of drugs. It analyzes the way the human body deals with a drug after it has been administered, and the transportation of the drug to the specihc site for drug-receptor interaction. For example, a person has a headache and takes an aspirin to abate the pain. How does the aspirin travel from our mouth to reach the site in the brain where the headache is and act to reduce the pain ... 

The present volume of the series Methods and Principles in Medicinal Chemistry focuses on the impact of pharmacokinetics and metabolism in Drug Design. Pharmacokinetics is the study of the kinetics of absorption, distribution, metabolism, and excretion of drugs and their pharmacologic, therapeutic, or toxic response in animals and man. 

Laplace transformation is particularly useful in pharmacokinetics where a number of series first-order reactions are used to model the kinetics of drug absorption, distribution, metabolism, and excretion. Likewise, the relaxation kinetics of certain multistep chemical and physical processes are well suited for the use of Laplace transforms. 

Pharmacologic factors include (1) the kinetics of absorption, distribution, and elimination (2) the ability of the drug to be delivered to the site of infection (3) the potential toxicity of an agent and (4) pharmacokinetic or pharmacodynamic interactions with other drugs. 

Lee, P. Effect of nonuniform initial drug concentration distribution on the kinetics of drug release from glassy hydrogel matrices. Polymer 25 973-978, 1984. 

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. 

The introduction and use of primary cells for ADMET assays may make a valuable contribution to the level and quality of information obtained from the tests. Absorption, distribution, metabolism, and excretion (ADME) encompass the disposition of a pharmaceutical compound within an organism. These four criteria influence the levels and kinetics of drug exposure to tissues and hence influence the performance and pharmacological activity of a compound as a drug. 

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. 

Vitreous 12) Distribution and elimination in vitreous 12) Kinetics of drugs in rabbit vitreous and clinical data... 

E. Nelson, Kinetics of drug absorption, distribution, metabolism and excretion. J Pharm Sci 50 181-182 (1961). 

Besides the kinetics of drug transport, also the equilibrium distribution of polar compounds (preferably in the aqueous phases), compounds with intermediate lipophilicity (in both phases), and lipophilic compounds (preferably in the lipid phases)... 

As in all standard two-compartment models, the rate of drug distribution transport between the two compartments is taken to follow first-order or linear kinetics. 

The rate of drug distribution transport between the central compartment (containing the systemic circulation) and any tissue compartment is taken to follow first-order or linear kinetics. This means that the rate of drug transport from compartment 1 to any other compartment is proportional to the amount of drug in compartment 1. Similarly, the rate of drug transport... 

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