Pharmacokinetics of drug distribution

Pharmacology, the study of agents and their actions, can be divided into two branches. Pharmacodynamics is concerned with the effects of a drug on the body and, therefore, encompasses dose-response relationships as well as the molecular mechanisms of drug activity. Pharmacokinetics, on the other hand, is concerned with the effect of the body on the drug. Drug metabolism, transport, absorption, and elimination are components of pharmacokinetic analysis. 

In this section, pharamacokinetics will be introduced by first considering the simplest situation an agent is introduced into a single body compartment from which it is also eliminated. While quite sophisticated compartmental models can be developed from this basic construct, it is frequently difficult 

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Pharmacokinetics of Drug Distribution Table 7.3 Scaling dependencies for various variables... 

The administration of a drug by a rapid intravenous injection places the drug in the circulatory system where it is distributed (see section 2.7.1) to all the accessible body compartments and tissues. The one compartment model (Figure 8.3(a)) of drug distribution assumes that the administration and distribution of the drug in the plasma and associated tissues is instantaneous. This does not happen in practice and is one of the possible sources of error when using this model to analyse experimental pharmacokinetic data. 

Roberts MS, Donaldson JD, Rowland M. Models of hepatic elimination a comparison of stochastic models to describe residence time distributions and to predict the influence of drug distribution, enzyme heterogeneity, and systemic recycling on hepatic elimination. J Pharmacokinet Biopharm 1988 16 41-83. 

Absorption of a drug into the theoretical central or main compartment may be followed by distribution into one or more peripheral compartments, or the drug may undergo excretion or metabolism from the central compartment. While compartmental analysis of drug distribution can be informative, it is beyond the scope of this book. For more details on the effect of multicompartmental distribution of a drug on pharmacokinetics, see references in the Bibliography. 

Pharmacokinetics Ribavirin is effective orally and intravenously. Its current use is as an aerosol in certain respiratory viral conditions, such as the treatment of RSV infection. Studies of drug distribution in primates showed retention in all tissues, except brain. The drug and its metabolites are eliminated in the urine. 

The three estimates of distribution volume that we have encountered have slightly different properties (24). Of the three, Vd(ss) has the strongest physiologic rationale for multicompartment systems of drug distribution. It is independent of the rate of both drug distribution and elimination, and is the volume that is referred to in Equations 3.1 and 3.2. On the other hand, estimates of V ( area) most useful in clinical pharmacokinetics, since it is this volume that links elimination clearance to elimination half-life in the equation... 

Diseases such as hepatic or renal diseases can influence the incidence of ADRs by altering the pharmacokinetics of drugs, such as absorption, distribution, metabolism, or excretion. 

The recently discovered title compound BMY-22089, 167, is more potent than the natural products compactin and mevinolin in lowering the serum cholesterol levels in both animals and man by inhibiting the action of enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) which determines the biosynthesis of cholesterol. It has been prepared in 20% overall yield in various steps starting with the tetrazol 168 (equation 58), for pharmacokinetic and drug distribution studies. 

Atkinson A J, Ruo T, Frederiksen M C 1996 Physiological basis of multicompartmental models of drug distribution. Trends in Pharmacological Sciences 12 96-101 Baggot J D 1990 Pharmacokinetic-pharmcodynamic relationship. Annals de Recherches Veterinaires 21(suppl) 29-40... 

Many factors have a profound influence on the pharmacokinetics of drugs and consequently on a patient s pharmacological response (Box 33-1). For example, the consideration of the patient s history, with particular emphasis on theirpathophysiological state and adjunct drug therapy, is essential at the initiation of drug therapy and TDM. Other important factors include how a drug is absorbed, distributed, metabolized, cleared by the Liver, biotransformed, and excreted. 

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