In a two-compartment pharmacokinetic model, if k12 is much larger than k21, what is the expected distribution pattern?

• A. Equal exchange between compartments
• B. Rapid movement from central to peripheral with slower return
• C. Slow movement from central to peripheral
• D. No distribution between compartments

Answer: (B)

In a two-compartment pharmacokinetic model, how the drug moves between the central (blood) and peripheral (tissue) compartments depends on the inter-compartment rate constants k12 (central to peripheral) and k21 (peripheral to central). When k12 is much larger than k21, the transfer from the central compartment to the peripheral one happens much more quickly than the reverse transfer. That means the drug rapidly leaves the central compartment and distributes into the peripheral compartment, but it returns to the central compartment only slowly because the backflux is small. The net effect is a rapid distribution into the peripheral compartment with a slower rate of return to the central compartment, making the peripheral compartment act as a reservoir during the distribution phase.