Table 2.

Rate constants for the hydrolysis of codrugs 1-2, 5, and 9–14 in 80% rat plasma and 80% human plasma at 37°C.

	Rat plasmaa		Human plasmaa
Compd	t 1/2 (min)	K obs (min−1)	t 1/2 (min)	K obs (min−1)
1	immediate hydrolysis	—	3.2  (±0.1)	0.217  (±6 × 10−3)
2	2.7  (±0.1)	0.257  (±8 × 10−3)	15.1  (±0.4)	0.046  (±1 × 10−3)
5	4.7  (±0.1)	0.150  (±0.01)	7.3  (±0.3)	0.100  (±0.01)
9	46.8  (±1.4)	0.010  (±0.20 × 10−3)	69.6  (±1.4)	0.015  (±0.44 × 10−3)
10	36.6  (±1.6)	0.019  (±0.85 × 10−3)	65.4  (±1.6)	0.011  (±0.26 × 10−3)
11	115.2  (±11.0)	0.002  (±0.07 × 10−3)	315.0  (±4.6)	0.006  (±0.24 × 10−3)
12	93.0  (±10.2)	0.003  (±0.17 × 10−3)	263.4  (±1.9)	0.007  (±0.14 × 10−3)
13	55.8  (±10.5)	0.003  (±0.11 × 10−3)	203.4  (±0.6)	0.030  (±0.75x10 − 3)
14	69.6  (±3.5)	0.010  (±0.50 × 10−3)	90.0  (±2.7)	0.008  (±0.24 × 10−3)

^aValues are means of three experiments, standard deviation is given in parentheses.