Two compartment drug

This refers to the observable behaviour of a drug that moves relatively slowly (in both directions) between the central compartment (blood, along with other highly-vascularised tissues to which drug distributes rapidly) and other tissues and organs into which a drug distributes extensively. Because of this relatively slow movement, data from plasma samples that are collected at earlier time points after an IV injection of drug indicate that the drug is being lost from plasma as a result of two simultaneous exponential processes, i.e. distribution and elimination. Once distribution equilibrium is reached, drug is then only being lost from the central compartment as a result of a single exponential process (elimination).

When data are plotted versus time on a logarithmic concentration axis, the curve resembles a hockey stick, with the curved blade indicating where both distribution and elimination are occurring, and the point where the blade straightens out and becomes the straight handle is the point at which distribution reaches equilibrium and net loss of drug from the plasma is due solely to elimination (see the entry for exponential curve for further details).

The other impact of slow movement between compartments is that the loss of drug from the plasma due to (hepatic and/or renal) elimination is slower than it otherwise could have been, due to the fact that when drug is lost from the plasma, more drug redistributes only slowly from the tissues back to the plasma to replace some of the drug that has been eliminated. This puts a “brake” on the elimination of drug from the central compartment, and prolongs the time it takes for drug to be cleared from the body; the same drug could be cleared faster, and would have a shorter half-life for elimination, if drug moved more rapidly from tissues back into the plasma. This point is discussed in more depth under the manual entry for half-life of elimination.