Drug availability to noneliminating tissues and sites of action following an intravenous dose.

It is shown that for drugs with high clearance, administered as an intravenous (iv) bolus, the amount of drug available to noneliminating tissues may be significantly less than the administered dose. This arises as a result of recirculation and elimination of some drug within an eliminating circuit, without contact of the drug with tissues outside the eliminating circuit. The same effect also influences drug availability to noneliminating tissues following an oral dose. The relative availability of a drug to sites of action and drug toxicity are also discussed and shown to depend on clearance and blood flow to these sites.