17. Pharmacokinetics and Pharmacodynamics of Drugs

Definition: study of the absorption, distribution, metabolism, and excretion of drugs in the body

Absorption

Drugs administered extravascularly must be absorbed across biologic membranes to reach the systemic circulation.

Extent and rate of drug absorption are determined by physiochemical properties, formulation, and route of administration.

Non-intravenous administration may result in reduced absorption.

Enteral absorption may be reduced due to gut hypomotility, hypoperfusion, changes in gastrointestinal (GI) pH, and enteral feeding.

Subcutaneous/intramuscular/transdermal absorption may be reduced due to hypoperfusion of muscles, skin, and splanchnic organs.

Bioavailability (F)—the fraction of unchanged drug that reaches the systemic circulation following administration

Drugs given intravenously have 100% bioavailability.

Drugs administered orally have reduced bioavailability primarily due to incomplete absorption and first-pass elimination.

First-Pass Effect—drug removed from the blood or plasma via GI and hepatic enzymes following absorption from the GI tract, prior to reaching the systemic circulation

Results in a significant reduction in bioavailability

Drugs that undergo first-pass effect will require dose reductions when given intravenously.

Examples: diltiazem, labetolol, lidocaine, metoprolol, morphine, nitroglycerin, verapamil, propranolol

Distribution

The passing of drug molecules from the blood into tissues and organs

V_d is affected by drug permeability, protein binding, tissue binding, and organ perfusion

Table 17.1.1 describes the pharmacokinetic factors that influence C_p and V_d

Drugs tend to have an increased C_p if they have low lipid solubility, increased plasma protein binding, or decreased tissue binding and as a result will have a reduced V_d.