Summary of "FARMACOCINETICA clase"

Main ideas & lessons (Pharmacokinetics overview)

• Pharmacology is mainly divided into two complementary fields:

  • Pharmacokinetics (PK): what the body does to the drug (what happens to the drug after administration).
  • Pharmacodynamics (PD): what the drug does to the body (effect related to dose/concentration and mechanism of action).

• Central objective of treatment: after administration, the drug should reach plasma, then distribute through the body to produce an effect.

• PK is dynamic and time-dependent, varying with:

  • administration route and formulation
  • dose
  • pathology (acute vs chronic)
  • patient conditions (e.g., organ function, age, hemodynamics)
  • drug-specific properties (lipophilicity, protein binding, ionization state)

Pharmacokinetic stages (LME)

The course uses the acronym LME:

L — Liberation (release)

• The drug must detach from its pharmaceutical form (tablet, capsule, injection, aerosol, suppository, ovule, etc.).
• Different pharmaceutical forms imply different release behaviors.

A — Absorption

• After release, the drug must be absorbed to become available in the bloodstream.
• Key concept: success depends on how much reaches circulation, not just the administered dose.
• Oral/non-IV routes require multiple steps before the drug reaches plasma.

D — Distribution

• Once in plasma, the drug moves into body compartments (tissues/cells) based on:
  • ability to cross barriers (e.g., blood-brain barrier)
  • lipophilicity vs water solubility
  • plasma protein binding (only the free fraction can act)
  • capillary permeability and tissue affinity
• Lipid-soluble drugs may accumulate in fatty tissues, causing longer-than-expected presence due to diffusion dynamics.

M — Metabolism (biotransformation)

• Usually primarily in the liver (enzymes transform drug into metabolites).
• Goal: facilitate elimination, often by increasing polarity/water solubility.

Includes:

• Phase 1: “functionalization” (e.g., oxidation/reduction/hydrolysis); often via cytochrome P450.
• Phase 2: “conjugation” using endogenous substrates (e.g., glucuronide, sulfate, acetyl, methyl, etc.); includes glucuronidation as a major example.

Enzyme activity is:

• saturable (limited capacity)
• affected by genetics, liver health, age/sex, and drug interactions
• modulated by:
  • enzyme induction (faster metabolism)
  • enzyme inhibition (slower metabolism)

E — Excretion

• Main route: kidneys/urine.
• Other elimination routes mentioned as complementary:
  • lungs (via exhalation/aspiration)
  • bile/feces (via remaining fractions or hepatobiliary elimination)
  • sweat/skin
  • breast milk
  • saliva/tears
  • hair/skin
• Renal excretion depends on:
  • glomerular filtration
  • tubular secretion
  • tubular reabsorption
• Requires renal system functionality; renal insufficiency requires dose adjustment.

Concentration–effect and exposure concepts

• PK is connected to dose/concentration achieved:

  • As concentration rises, effect increases until a maximum.
  • Then concentration falls as metabolism/excretion occur.

• Therapeutic range

  • Drug levels must stay between:
    • minimum effective concentration (above this → effectiveness)
    • minimum toxic concentration (below this → avoid toxicity)
  • Duration of effect = time concentration remains within the safe effective window.
  • Latency period may occur (especially oral routes) due to release and absorption time before measurable plasma concentration.

• PK graphs and parameters

  • Typical PK curve: plasma concentration vs time.
  • Important PK parameters:
    • AUC (Area Under the Curve): degree of exposure to the drug
    • Cmax (maximum concentration)
    • Cmin / trough (lowest/near-undetectable concentration)
    • Half-life (t½): time for concentration to reduce by half (also helps plan dosing intervals)

• Half-life and dosing interval

  • Dosing too far apart relative to half-life → levels drop below effectiveness.
  • Dosing too close → accumulation → potential toxicity.
  • Oral/non-IV routes differ graphically due to absorption time (often starting from ~0 and rising).

Routes and pharmaceutical forms: how they shape PK

• Administration route strongly affects absorption and the concentration–time profile, including:

  • intramuscular
  • subcutaneous
  • inhalation
  • oral
  • rectal
  • intrathecal (mentioned)
  • topical/thermal (mentioned broadly)

• Pharmaceutical form matters (e.g., oral solution vs tablet/capsule):

  • oral solution typically gives faster availability because it is already in solution
  • tablets/capsules must dissolve/release before absorption

• First-pass effect (oral route)

  • Drug absorbed into the portal vein goes to the liver first, where some fraction is metabolized before systemic availability.
  • This reduces the amount reaching systemic circulation compared with routes that bypass first-pass.

Distribution specifics (compartments, proteins, barriers)

• Distribution depends on:

  • protein binding (bound fraction is pharmacologically inactive)
  • free drug fraction being the relevant one for receptor action
  • ability to cross body barriers

• Volume of distribution (concept)

  • Treated as an apparent container where drug distributes.
  • Relationship: Vd ≈ dose / concentration achieved
  • Higher lipid solubility → larger apparent volume of distribution.

• Example logic given:

  • Very perfused organs (e.g., brain/heart/kidneys) may receive drug quickly; less perfused tissues (skin, fat) later/less.

Ionization, pH, and membrane crossing (Henderson–Hasselbalch)

• Drug forms can be:
  • Ionized (charged, hydrophilic, water soluble)
  • Non-ionized (uncharged, lipophilic, membrane-permeable)
• Passage across membranes is easier for non-ionized/lipophilic forms.
• pH affects ionization ratio using the Henderson–Hasselbalch concept.
• Example:
  • In acidic gastric juice, weak acids/bases shift ionization balance, affecting which form predominates and therefore absorption/crossing.

Bioavailability & bioequivalence (formulation equivalence)

Bioavailability

• Fraction of administered dose reaching systemic circulation in an active form.
• It differs by route (IV gives near-complete availability in principle) and by formulation/absorption/metabolism.

Bioequivalence

• Used to confirm that two formulations (reference vs generic/comparator) behave similarly, especially for drugs with narrow safety margins.

• Cross-over study concept (as described):

  • two populations
  • give reference to one population and comparator to the other
  • allow washout/clearance
  • switch: reference to the second population and comparator to the first
  • compare PK profiles (curves) using similarity in AUC, half-life, and overall behavior

• Caution emphasized:

  • Even if PK profiles look similar, one product may cross into unsafe ranges (below minimum toxic concentration considerations).
  • Linear relationship between dose and AUC is important for assessing proper behavior.

Metabolism details & interactions

• Metabolism is one-directional and enzyme-mediated (mainly liver).
• It generally increases polarity so drugs can be excreted.
• Cytochrome P450 (Phase 1) metabolizes a large proportion of drugs (stated: up to 85%).

• Enzyme induction/inhibition

  • Induction → faster clearance (drug disappears sooner)
  • Inhibition → slower clearance (drug persists longer)

• Drug interactions

  • Competition for the same enzymes can reduce metabolism of one drug when another occupies the enzyme (described as a “roundabout” analogy).

Excretion details & renal dependence

• Renal elimination relies on kidney processes and can be altered by age/pregnancy/conditions.
• Strategies noted:
  • pH manipulation to shift ionized vs non-ionized fractions to improve excretion (conceptual approach).
• If kidneys can’t excrete properly → dose adjustment needed.

Speakers or sources featured

• No named speakers or external sources are explicitly identified in the subtitles.

Category

Educational

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