Abstract
The extraction ratio (Ec) and the mean cycle times (t^-c) for single systemic and pulmonary circulation were evaluated for 115 drugs in man. Heparin and fluorohydrocortisone, which have the smallest t^-c values (about 1min) show the small Ec values (close to zero). This result suggests that these drugs circulate through the body restricted within the blood vessels. The theoretical considerations indicate that the clearances defined by Ai (∞)/AUC differ from EiQi, where Ai(∞) is the amount eliminated by organ i, AUC is the area under the plasma concentration curve, Ei is the extraction ratio and Qi is plasma flow rate through organ i. The hepatic extraction ratios (Eh) of alprenolol, metoprolol and propranolol calculated from intravenous data alone are large (above 80%). It is also shown that the steady-state volume of distribution (Vss) is rather independent of hepatic and renal extraction ratios, while the mean residence time (MRT) is considerably affected by change of these ratios.
