TABLE 4

Simulated PK parameters for bufuralol and dextromethorphan

Dose of bufuralol (60 mg) or dextromethorphan (30 mg) simulation for 24 h. Geometric means reported with fold difference between simulation and traditional Sim_pH7.4 given in parentheses.

Simulation	Bufuralol				Dextromethorphan
Simulation	CL_int,u	CL	C_max	AUC	CL_int,u	CL	C_max	AUC
	μl/min/mg protein	l/h	μg/l	μg/l·h	μl/min/mg protein	l/h	μg/l	μg/l·h
Sim_{pH 7.4}	20.0	49.02	209.02	1223.91	36.0	500.47	5.16	59.94
Sim_{pH 7.4, FI}	20.0 (1.0)	118.70 (2.4)	116.84 (0.6)	505.47 (0.4)	36.0 (1.0)	1085.39 (2.2)	2.61 (0.5)	27.64 (0.5)
Sim_{pH 7, FI}	8.3 (0.4)	64.72 (1.3)	180.45 (0.9)	927.01 (0.8)	19.4 (0.5)	630.14 (1.3)	4.28 (0.8)	47.61 (0.8)
Observed	—	66.96	164^{^a}	896^{^a}	—	845.1	3.49^{^b}	35.5^{^b}

CL, clearance calculated as dose/AUC; CL_int,u, in vitro intrinsic clearance corrected for fraction unbound in microsomes.
↵^a Dayer et al. (1982).
↵^b Chi et al. (2013).