Affecting Drug Distribution

Many laws have been enacted over the last century that affect drug distribution and administration. Those included here are the Pure Food and Drug Act Harrison Narcotic Act Pure Food, Drug, and Cosmetic Act and the Comprehensive Drug Abuse Prevention and Control Act. These laws control the use of the three categories of drugs in the United States (prescription, nonprescription, and controlled substances). 

Although the impact of transporters on absorption appears to be moderate there is increasing evidence showing that transporters can significantly affect drug distribution, in particular for low permeable compounds. In this context transporter assays need to be prioritized for compounds with medium to low passive permeability. 

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. 

Regional blood flow changes also occur in pregnant women and can affect drug distribution and elimination. Blood flow increases to the uterus, kidneys, skin, and mammary glands, with a compensatory decrease in skeletal muscle blood flow. At full term, blood flow to the uterus represents about 20-25% of cardiac output and renal blood flow is 20% of cardiac output (15). There is increased blood flow to the skin to dissipate the additional heat produced by the fetus (16). Blood... 

Understanding the physiology of lactation and pharmacokinetic factors affecting drug distribution, metabolism, and elimination can assist the clinician with more appropriate... 

Although the general principles discussed here apply to all membranes, it is important to recognize that physiological (e.g., specific cell types, blood flow, and permeability) and molecular (e.g., uptake or efflux transporters) distinctions among tissue barriers can differentially affect drug distribution, which may be associated with efficacy or toxicity (Figure 7.10). 

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