On pharmacokinetics in target tissues.

Based on a two-compartment organ model the total exposure in a target tissue, the mean tissue residence time and the peak time of the tissue concentration are evaluated in terms of tissue to blood partition coefficient and permeability coefficient (membrane permeability) of the drug, as well as the organ volume and blood flow. The total exposure is dependent upon the partition coefficient whereas the mean residence time is also affected by the permeability coefficient of the target organ. The peak time of tissue concentration following bolus intravenous injection appears to be mainly determined by the mean organ transit time and the time course of blood concentration. A tissue specific therapeutic ratio is defined using the concept of total exposure and the advantages of a local route of drug administration are discussed in this respect.