Table 2.

Pharmacokinetic parameters of prodrugs and parent 3 in male Sprague-Dawley rats (180–200 g) by i.g. (20 mg/kg) dosing and 3 by i.v. (2 mg/kg) in 10% PEG400.

Parameter	Compound									3(iv)
	5	6	7	8	9	10	12	13	3
AUC(0-t) ng·L/mL	521.7 ± 133.6	157.9 ± 42.94	354.2 ± 105.6	588.9 ± 72.06	384.1 ± 6.21	1296.5 ± 437.6	775.6 ± 162.9	477.8 ± 128.7	966.3 ± 219.7	558.4 ± 8.71
CL (L/h/kg)	0.033 ± 0.006	0.102 ± 0.020	0.046 ± 0.013	0.034 ± 0.004	0.037 ± 0.001	0.016 ± 0.007	0.026 ± 0.005	0.040 ± 0.010	0.020 ± 0.005	0.003 ± 0.0001
Vd (L/kg)	0.252 ± 0.130	0.669 ± 0.422	0.373 ± 0.193	0.102 ± 0.011	0.467 ± 0.063	0.045 ± 0.017	0.049 ± 0.020	0.123 ± 0.058	0.079 ± 0.039	0.008 ± 0.002
Cmax (ng/mL)	284.1 ± 74.73	80.9 ± 18.80	254.6 ± 32.45	398.5 ± 29.00	163.6 ± 13.56	621.5 ± 79.67	529.0 ± 192.9	191.1 ± 2.48	530.7 ± 120.8	−
Tmax (h)	0.50	0.38	0.25	0.50	0.25	0.75	0.50	0.75	0.58	−
MRT(0-t) (h)	3.092 ± 0.454	2.658 ± 0.681	3.769 ± 0.063	1.517 ± 0.207	3.581 ± 0.307	1.793 ± 0.181	1.286 ± 0.085	2.136 ± 0.123	1.983 ± 0.478	1.235 ± 0.168
F(%)	10.3	3.3	7.2	12.4	7.5	25.7	15.8	9.8	17.3	−