Wagner J G, Szpunar G J, Ferry J J
Biopharm Drug Dispos. 1985 Apr-Jun;6(2):177-200. doi: 10.1002/bdd.2510060209.
For single bolus administration, intermittent bolus administrations to steady-state, a single dose as a zero order input, intermittent zero order inputs to steady-state, and continuous zero order input to steady-state, and for both simple Michaelis-Menten elimination and parallel Michaelis-Menten and first order elimination, the appropriate equations are given for the areas, AUC 0-oo or AUC 0-tau, steady-state concentrations, and clearances. Some 20 new equations have been derived. For the case of first order input and Michaelis-Menten elimination, no solution is given but the effect of input rate on systemic availability is reported following some numerical integrations. The effect of slow input in reducing systemic bioavailability when Michaelis-Menten elimination kinetics are operative is stressed and the implications of this in the field of sustained-release medication mentioned.
对于单次大剂量给药、间歇性大剂量给药至稳态、作为零级输入的单剂量、间歇性零级输入至稳态以及连续零级输入至稳态,以及对于简单的米氏消除和平行的米氏及一级消除,给出了关于血药浓度-时间曲线下面积(AUC 0-∞或AUC 0-τ)、稳态浓度和清除率的适当方程。已经推导出约20个新方程。对于一级输入和米氏消除的情况,未给出解析解,但在进行一些数值积分后报告了输入速率对全身可用性的影响。强调了在米氏消除动力学起作用时缓慢输入对降低全身生物利用度的影响,并提及了这在缓释药物领域的意义。