. 2016 Feb 10;151(1):57–70. doi: 10.1093/toxsci/kfw022

TABLE 5.

Chemical-Specific Parameters for the Human PBPK Model

	Chemical^a
Parameter	MMI	PTU	BP2	MBT	TCS	RSC	Source
IC₅₀ (μM)	0.025	0.12	0.16	0.45	142	253	Measured, Paul et al. (2014)
I_Max (% activity)	0.9084	0.9426	0.9059	0.9684	0.511	0.229	Measured, Paul et al. (2014)
Clearance (ml/min)	80.9	270.0	15.8	25.5	48.3	139.1	Measured and predicted^b
Absorption rate constant (k_a; 1/min)	0.0087	0.0078	0.009	0.012	0.0438	0.0096	Predicted, GastroPlus
Tissue to Plasma PCs
Kidney (P_Kid)	0.81	0.42	0.20	0.88	3.98	0.82	Predicted, GastroPlus
Liver (P_Liv)	0.80	0.42	0.18	1.28	6.55	0.88	Predicted, GastroPlus
Rest of body (P_Rap)- for lung	0.82	0.43	0.23	0.41	0.91	0.76	Predicted, GastroPlus
Muscle (P_Mus)	0.78	0.36	0.13	0.83	4.02	0.79	Predicted, GastroPlus
Skin (P_Skin)	0.75	0.51	0.35	1.14	4.99	0.81	Predicted, GastroPlus
Yellow marrow (P_Slow)	0.21	0.21	0.18	1.79	23.85	0.37	Predicted, GastroPlus
Adipose (P_Fat)	0.21	0.21	0.18	1.79	23.85	0.37	Predicted, GastroPlus
Brain (P_Brain)	0.87	0.47	0.20	1.92	10.48	1.03	Predicted, GastroPlus
Thyroid (P_Thyroid)	2.80	2.21	0.20	0.88	3.98	0.82	Predicted, GastroPlus or fitted^c

^aChemical abbreviations: MMI, methimazole; PTU, 6-propylthiouracil; BP2, benzophenone-2; MBT, 2-mercatobenzothiazole; TCS, triclosan; RSC, resorcinol.

^bTotal clearance was taken for each chemical as a function of t_1/2 and V_d. Clearance for MMI, PTU, and TCS used measured values for t_1/2 and V_d. Clearance for BP2, RSC, and MBT used predicted V_d from ADMET Predictor software and t_1/2 predicted using the equation from Sarver et al. (1997). See text for additional details.

^cThe thyroid to plasma PC was set to that of kidney to plasma PC with the observation that these values are similar (Merrill et al., 2005). For MMI and PTU, this value was adjusted to that in the rat used to fit measured data showing higher concentrations of the drugs in the thyroid compared with within blood.