Effect of arterial-venous plasma concentration differences on the determination of mean residence time of drugs in the body.

Using dogs or rabbits as model animals the effect of arterial-venous plasma concentration differences of propranolol, procainamide, griseofulvin, furosemide and theophylline on the determination of mean residence time (MRT) following intravenous administration was evaluated using standard methods. The MRT values calculated from femoral venous data were always higher (ranging from 1.5 to 109%) than those from femoral arterial data. The differences were mainly attributed to the additional residence time of drugs in the sampling tissue (leg). From a physiological point of view it appears generally more logical to assume that only the MRT calculated from arterial data using conventional methods represents the "true" MRT in the body. The potential pharmacokinetic significance of the present findings is discussed. New approaches, which eliminates the effect of arterial-venous plasma concentration differences on the MRT determination, are proposed.