TABLE 2

Covalent binding and metabolic conversion of [¹⁴C]rimonabant in human liver microsomal incubations with and without reactive metabolite trapping agents

Test Compound	Trapper	NADPH (Yes/No)	Covalent Binding ± S.D.^{^a}	Conversion^{^b}	Corrected Covalent Binding^{^c}	Fraction Covalent Binding^{^d}
			pmol eq/mg protein	%	pmol eq/mg protein
[¹⁴C]Rimonabant	No trapper	Yes	920 ± 24	49	920	0.19
	No trapper	No	10 ± 0.3	NA	NA	NA
	Cyanide	Yes	432 ± 17	37	578	0.12
	Glutathione	Yes	811 ± 59	47	851	0.17
	Methoxylamine	Yes	182 ± 6.1	14	633	0.13

NA, not applicable.
a Means of three incubations ± S.D.
b Metabolic conversion of [¹⁴C]rimonabant measured by LC-RAD.
c Covalent binding values measured in the incubations with trappers are corrected for the difference in percentage conversion of parent compared with the no trapper incubation with NADPH [i.e. corrected covalent binding = (covalent binding in the presence of trapper/conversion in the presence of trapper) × conversion in the absence of trapper].
d The fraction covalent binding is calculated as follows: fCVB = covalent binding × protein concentration/(total radioactivity in incubation × conversion).