Table 2

The effect of various potential inhibitors on the carboxylesterase-mediated production of SN-38 from CPT-11

Inhibitor	Experiment	Mean SN-38 formed (ng/ml/15 min)	Mean % of Control (uncorr.)	Mean % of Control (boiled corr.)
Control microsomes	1	17.2 ± 0.1	100	100
25 μM 5-FU	1	16.8 ± 0.1	97.8	97.6
25 μM NaF	1	15.8 ± 0.2	91.9	91.0^2-c
100 μM NaF	1	15.1 ± 0.1	87.6	86.3^2-d
500 μM NaF	1	11.8 ± 0.1	68.7	65.4^2-d
25 μM BNPP	1	1.9 ± 0.1	10.8	1.3^2-d
100 μM BNPP	1	1.9 ± 0.1	11.1	1.6^2-d
25 μM probenecid	1	15.1 ± 0.1	88.1	86.8^2-c
Phosphate control	1	1.6 ± 0.1	9.3	−0.5^2-d
Boiled microsomes	1	1.7 ± 0.2	9.7	0.0^2-d
Control microsomes	2	15.1 ± 0.5	100	100
44 μM HMB^2-a	2	14.8 ± 0.3	101	101
21 μM CMB^2-a	2	15.4 ± 0.6	105	106
24 μM loperamide^2-a	2	13.6 ± 0.5	93.2	92.5
Control with MeOH	2	14.6 ± 0.2	96.8	96.5
25 μM EtOH	2	14.4 ± 0.1	95.6	95.1
100 μM EtOH	2	14.2 ± 0.3	94.1	93.5
26 μM BNPP	2	1.6 ± 0.1	10.4	1.5^2-b
Phosphate control	2	1.4 ± 0.0	9.4	0.3^2-d
Boiled microsomes	2	1.4 ± 0.1	9.1	0.0^2-c
Control microsomes	3	11.3 ± 0.2	100	100
36 μM caffeine^2-a	3	11.0 ± 0.1	97.7	97.5
32 μM metoclopramide^2-a	3	10.3 ± 0.1	91.6	90.9^2-c
28 μM acetaminophen^2-a	3	10.5 ± 0.2	93.6	93.0^2-b
Control with MeOH	3	10.6 ± 0.1	94.0	93.4
26 μM Coumarin^2-a	3	10.5 ± 0.2	99.2	99.2
39 μM ASA^2-a	3	10.5 ± 0.4	99.6	99.6
26 μM BNPP	3	1.2 ± 0.1	11.1	3.3^2-d
Phosphate control	3	0.9 ± 0.1	8.0	−0.1^2-d
Boiled microsomes	3	0.9 ± 0.0	8.0	0.0^2-d
Control microsomes	4	11.1 ± 0.4	100	100
25 μM Physostigmine^2-a	4	2.9 ± 0.2	31.1	23.4^2-b
25 μM Dexamethasone^2-a	4	9.0 ± 0.8	96.9	96.6
Control with MeOH	4	9.3 ± 0.8	83.3	81.8
25 μM cisplatin^2-a	4	9.7 ± 1.8	105	106
25 μM prochlorper. Susp.^2-a	4	8.7 ± 1.4	93.7	93.0
26 μM BNPP	4	1.2 ± 0.0	10.9	2.8^2-c
Phosphate control	4	0.9 ± 0.0	8.4	0.1^2-c
Boiled microsomes	4	0.9 ± 0.1	8.3	0.0^2-c

Standard incubation conditions of 15 min and 1 mg/ml were used at a CPT-11 concentration of 10 μM.
↵2-a Use MeOH containing control value.
↵2-b p < 0.05.
↵2-c p < 0.01.
↵2-d p < 0.001.