Cutler D J
J Pharm Sci. 1986 Dec;75(12):1141-4. doi: 10.1002/jps.2600751205.
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.
结果表明，对于高清除率的药物，以静脉推注方式给药时，非消除组织可利用的药量可能显著少于给药剂量。这是由于在消除循环中部分药物的再循环和消除，而药物未与消除循环外的组织接触所致。同样的效应也会影响口服给药后药物对非消除组织的可利用性。还讨论了药物对作用部位的相对可利用性以及药物毒性，并表明其取决于这些部位的清除率和血流量。
