Huang J D, Oie S
J Pharmacokinet Biopharm. 1984 Feb;12(1):67-81. doi: 10.1007/BF01063611.
For a drug with concentration-dependent serum protein binding, the unbound fraction of drug decreases during the drug elimination process. The clearance of the drug at a given blood flow rate is lower than would be expected from the observed unbound fraction in venous blood from a noneliminating organ. Based on both the "well-stirred" and "parallel tube" models, simulations demonstrated that consideration of concentration-dependent binding during drug elimination is important when the intrinsic clearance is higher than the blood flow and when the unbound drug concentration is much greater than the dissociation equilibrium constant of the binding complex.
对于具有浓度依赖性血清蛋白结合的药物，在药物消除过程中，药物的游离分数会降低。在给定血流速率下，该药物的清除率低于根据非消除器官静脉血中观察到的游离分数所预期的值。基于“充分搅拌”模型和“平行管”模型的模拟表明，当内在清除率高于血流速率且游离药物浓度远大于结合复合物的解离平衡常数时，在药物消除过程中考虑浓度依赖性结合很重要。
