Tema 3. FARMACOCINÉTICA; Distribución.

Pharmacokinetics: Distribution of Drugs

Understanding Drug Distribution

• The distribution of a drug refers to its dispersion throughout the body, allowing access to various organs for action or elimination.

• In pregnant women, drug distribution is particularly significant as it can explain delays in onset or termination of effects.

• Drugs in plasma can travel freely or bound to plasma proteins; most commonly, they bind to albumin and other proteins like alpha-1 acid glycoprotein.

Factors Influencing Protein Binding

• The binding of drugs to plasma proteins varies significantly, affecting the percentage of free drug available for therapeutic action.

• Conditions such as liver and kidney diseases can alter protein levels, impacting drug binding and potentially leading to variations in drug effects.

Mechanisms of Drug Movement

• Drugs dissolved in blood move from capillaries into tissues following concentration gradients; lipophilic drugs easily penetrate well-perfused organs but struggle with poorly perfused ones.

• Certain tissues may accumulate high concentrations of specific drugs, which could reduce their effectiveness at intended sites due to lower local concentrations.

Special Barriers and Their Implications

• Areas like the central nervous system (CNS), eyes, fetal circulation, and breast milk have unique transport mechanisms that complicate drug delivery.

• The apparent volume of distribution (Vd) is calculated by dividing the amount of drug administered by its plasma concentration; it indicates how extensively a drug disperses throughout body compartments.

Volume of Distribution Insights

• A low Vd suggests strong protein binding while a high Vd indicates extensive tissue uptake; this metric aids in determining effective dosing strategies.

• Various factors such as edema or obesity can necessitate dosage adjustments based on changes in Vd.

Models of Drug Distribution

• Three general models describe drug distribution:

• One-compartment model: Rapid uniform distribution across the body.

• Two-compartment model: Quick diffusion into a central compartment followed by slower movement into peripheral areas.

• Three-compartment model: Slow release from specific tissues after initial administration.