Tema 2. FARMACOCINÉTICA; Absorción.

Understanding Pharmacokinetics and Drug Absorption

Overview of Pharmacokinetics

• Pharmacokinetics involves the processes a drug undergoes after administration, including absorption, distribution, metabolism, and excretion. These processes occur simultaneously.

Mechanisms of Drug Absorption

• Absorption refers to how drugs enter the body from their administration site, primarily through cellular membranes. Factors influencing this include lipophilicity and ionization.

Key Factors Affecting Absorption

• Lipid-soluble drugs with small molecular weight that are non-ionized can easily cross biological membranes.

Mechanisms of Crossing Membranes

• Drugs can traverse biological membranes via several mechanisms:

• Passive Diffusion: Most common method where drugs dissolve in lipid bilayers without energy expenditure.

• Filtration: Involves passage through aqueous channels for low molecular weight substances.

• Active Transport: Requires energy; proteins transport drugs across membranes.

Passive Diffusion Details

• The rate of passive diffusion is influenced by drug concentration; higher concentrations lead to faster diffusion until equilibrium is reached.

Ionization and pH Effects on Drug Absorption

• Many drugs exist as weak acids or bases in solution, affecting their ionization state based on pH.

• The Henderson-Hasselbalch equation relates pH to the ionization fraction, impacting how much drug crosses membranes.

Implications of pH Variations

• Altering pH can modify the amount of drug absorbed or eliminated, which is crucial for therapeutic outcomes.

Other Transport Mechanisms

• Filtration: Allows negatively charged substances to pass through membrane pores; positively charged substances require active transport.

• Endocytosis/Exocytosis: Enable large molecules to enter or exit cells by engulfing them in membrane vesicles.

Importance of Active Transport

• Active transport systems are vital in specific areas like the blood-brain barrier and renal tubules due to their ability to saturate and compete with other substances.

Factors Influencing Drug Absorption

• Physiological factors (age, pregnancy).

• Pathological conditions (diarrhea, vomiting).

• Iatrogenic factors (drug interactions).

Biodisponibility vs. Absorption

Bioequivalence of Drugs

Understanding Bioequivalence

• Bioequivalence is defined as the condition where two drugs reach the same concentration in blood within a similar timeframe. This is crucial since the effects of most drugs are closely related to their plasma levels.

• The concept of minimum effective concentration (MEC) refers to the lowest concentration needed to produce a therapeutic effect, while minimum toxic concentration (MTC) indicates the level at which toxic effects may occur.

• The difference between MEC and MTC defines the therapeutic window. Drugs with a narrow therapeutic margin have minimal differences between effective and toxic concentrations, making monitoring essential.

Plasma Level Dynamics

• Plasma levels of a drug are not constant; they fluctuate over time. A graph depicting these levels illustrates how drug concentration changes post-administration, particularly for oral medications.

• Key parameters from this plasma level curve include:

• Minimum Toxic Concentration (MTC)

• Minimum Effective Concentration (MEC)

• Maximum Concentration (Cmax), which correlates with peak drug effects.