3.14
Modelli Compartimentali: Modello a Due Compartimenti
Il modello a due compartimenti suddivide il corpo in compartimento centrale e compartimento periferico per tener conto delle diverse velocità di perfu…
Il modello a due compartimenti presuppone che i farmaci non siano distribuiti uniformemente in tutto il corpo perché il tasso di perfusione sanguigna varia tra i diversi organi e tessuti. Quindi, questo modello divide il corpo in scomparti centrali e periferici.
Il compartimento centrale comprende sangue e tessuti altamente perfusi dove il farmaco è rapidamente distribuito.
Il compartimento periferico è costituito da tessuti in cui la distribuzione del farmaco è lenta.
Dopo una singola dose in bolo EV, la concentrazione del farmaco è elevata nel plasma e bassa nei tessuti.
La distribuzione del farmaco tra i compartimenti è un processo di primo ordine definito da costanti di velocità, definite costante di trasferimento o micro costante.
A causa della distribuzione, la concentrazione del farmaco diminuisce rapidamente nel plasma e aumenta nei tessuti fino a raggiungere un equilibrio.
Successivamente, la concentrazione del farmaco diminuisce lentamente in entrambi i compartimenti a causa dell'eliminazione.
In breve, la concentrazione plasmatica del farmaco diminuisce in modo biesponenziale, dove il rapido declino iniziale è la fase di distribuzione o ɑ e il successivo declino è la fase di eliminazione o β.
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Q1: Why does the two-compartment model divide the body into central and peripheral compartments?
The two-compartment model accounts for varying blood perfusion rates among organs and tissues. The central compartment includes blood and highly perfused tissues where drugs distribute rapidly, while the peripheral compartment contains tissues with slower drug distribution. This division reflects the reality that drug distribution is not uniform throughout the body.
Q2: What happens to drug concentration immediately after an IV bolus dose?
Following a single IV bolus dose, drug concentration is initially high in plasma and low in tissues. The drug concentration rapidly declines in plasma while simultaneously increasing in tissues as distribution occurs. This rapid initial decline represents the distribution or alpha phase of plasma concentration change.
Q3: How does drug distribution between compartments follow first-order kinetics?
Drug distribution between the central and peripheral compartments is a first-order process defined by rate constants termed transfer constants or micro constants. These constants govern how quickly drug molecules move from highly perfused tissues to slower-perfused tissues, controlling the rate and extent of drug redistribution throughout the body.
Q4: What occurs when drug concentration reaches equilibrium between compartments?
Once equilibrium is reached between central and peripheral compartments, drug concentration stops changing due to distribution. After this point, both compartments experience a slow, simultaneous decline in drug concentration due to elimination processes. This slower phase is called the elimination or beta phase.
Q5: Why does plasma drug concentration decline bi-exponentially in the two-compartment model?
Plasma drug concentration declines bi-exponentially because two distinct processes occur sequentially. The rapid initial decline represents the distribution or alpha phase as drug moves from plasma to tissues. The subsequent slower decline represents the elimination or beta phase after equilibrium is established and drug is removed from both compartments.
Q6: How does the two-compartment model differ from assuming uniform drug distribution?
The two-compartment model recognizes that blood perfusion rates vary among different organs and tissues, preventing uniform drug distribution. By dividing the body into central and peripheral compartments with different distribution rates, the model accurately predicts how drug concentration changes over time in plasma and tissues, rather than assuming instantaneous equilibrium.
Q7: What is the relationship between transfer constants and drug movement in compartmental analysis?
Transfer constants, also called micro constants, quantify the rate of drug movement between central and peripheral compartments during the first-order distribution process. These constants determine how quickly drug redistributes from highly perfused tissues to slower-perfused tissues and influence the duration and shape of the distribution phase in plasma concentration profiles.