One-Compartment Model with Extravascular Administration

One Compartment Model with Extravascular Administration describes drug absorption, distribution, and elimination after oral or IM dosing.

Definition of One-Compartment Model with Extravascular Administration

• Extravascular administration refers to all non-intravenous routes where the drug is not directly injected into the bloodstream. It includes:
  • Oral (PO)
  • Intramuscular (IM)
  • Subcutaneous (SC)
  • Inhalation, rectal, transdermal, etc.

Process

1. The drug is administered outside the bloodstream.
2. It undergoes an absorption phase before reaching systemic circulation.
3. The rate and extent of absorption depend on route of administration and physiochemical properties of the drug.
4. After absorption, the drug follows the same distribution and elimination as in the IV model.

Pharmacokinetics of Extravascular Administration

• The plasma concentration at time t is given by:
• $C = \frac{F D}{V_d} \left( \frac{k_a}{k_a – k_e} \right) \left( e^{-k_e t} – e^{-k_a t} \right)$
• Where:
  • F = Bioavailability (fraction of drug that reaches circulation)
  • D = Dose administered
  • V_d​ = Volume of distribution
  • k_a​ = Absorption rate constant
  • k_e​ = Elimination rate constant

Bioavailability (F)

• Since not all of the drug reaches systemic circulation, the bioavailability (F) is an important parameter.
• $F = \frac{AUC_{\text{extravascular}}}{AUC_{\text{intravenous}}}$
• Where AUC is the area under the plasma concentration-time curve.

Key Features:

• C_max: Peak plasma concentration
• T_max: Time to reach C_max
• Absorption influences onset and intensity of action

Advantages:

• Convenient and non-invasive (e.g., oral)
• Lower risk of infection
• Some routes offer prolonged action (e.g., transdermal)

Limitations:

• Variable absorption due to physiological and biochemical factors
• First-pass metabolism (especially oral)
• Slower onset compared to IV routes

Examples of Extravascular Routes

1. Oral (PO) – Slow onset, may undergo first-pass metabolism.
2. Intramuscular (IM) – Faster than oral, but slower than IV.
3. Subcutaneous (SC) – Similar to IM but slightly slower.
4. Inhalation – Rapid absorption via the lungs.
5. Transdermal – Slow and prolonged release.

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