TABLE 2

Physiologically-based pharmacokinetic model-simulated pharmacokinetic parameters of HSP90 inhibitors in male Sprague-Dawley rats after a single intravenous administration

A1, B1, and C1 are low-affinity HSP90 inhibitors, whereas A2, B2, and C2 were their corresponding high-affinity inhibitors.

HSP90 Inhibitor	Dose	Predicted AUC_0–∞		Predicted V_ss		Predicted t_1/2
	mg/kg	nM × h	(Ratio)^{^a}	l/kg	(Ratio)^{^a}	h	(Ratio)^{^a}
A1	0.75	613	(1.4)	3.6	(1.2)	1.2	(0.92)
	2.5	1777	(1.2)	3.6	(1.7)	1.1	(0.84)
	7.5	6502	(1.3)	3.6	(1.7)	1.2	(0.90)
B1	2.5	1718	(1.2)	3.1	(1.7)	0.91	(0.72)
C1	2.5	1794	(1.2)	3.7	(2.0)	1.1	(0.90)
A2	0.75	623	(1.4)	1.7	(0.15)	1.2	(0.28)
	2.5	1784	(1.2)	1.7	(0.13)	1.3	(0.16)
	7.5	7150	(1.3)	1.7	(0.32)	1.1	(0.18)
B2	2.5	1735	(1.2)	1.9	(0.19)	0.85	(0.11)
C2	2.5	1759	(1.2)	3.0	(0.27)	0.89	(0.11)

↵^a The ratios of model-simulated to observed parameters are expressed in parentheses.