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. 2012 Mar 10;14(2):262–281. doi: 10.1208/s12248-012-9332-y

Table IV.

Predictive Approaches of Human Plasma Concentration–Time Profile

Method Equation Data required Dataset <twofold
Species-invariant time method (90) Inline graphic Inline graphic Inline graphic Plasma concentration–time profiles, dose, CL, and Vdss in at least two animal species All categories
Equivalent time: Inline graphic Inline graphic n = 2 (100) 100% (AUC)
Kallynochrons: Inline graphic Inline graphic n = 3 (90) 67% (CL)
Apolysichrons:Inline graphic Inline graphic
Dienetichrons: Inline graphic Inline graphic
C ss–MRT method (91,92) Inline graphic Inline graphic Plasma concentration–time profiles, dose, CL, and Vdss in at least two animal species n = 4 (92) 75% (AUC)
75% (C max)
50% (C min)
100% (t 1/2)
n = 4 (91) 100% (CL)
50% (CL)
75% (Vdss)
Human PK prediction using PBPK model (95,96) Predict K p (tissue composition-based method) or experimentally measure in rats and assume K p, u, rat = K p, u, human. For hepatically eliminated compounds: CLH is scaled from microsome or hepatocyte data. For renally eliminated compounds: Inline graphic . Oral absorption: GastroPlusTM Blood flow, in vitro intrinsic clearance, tissue-to-plasma ratios, B/P ratio, fraction unbound in plasma, solubility and permeability information n = 19 (96) 83% (CL)
50% (Vdss)
75% (t 1/2)
92% (AUC)
67% (C max)
100% (t max)