Table 1.

Kinetic constants for the biotransformation of CMV423 and rac-RPR 127025 in vitro.

Enzyme source	Pathway	Km (µm)	Vmaxa (pmol min−1 pmol−1 P450)
Human liver microsomesb	Hydroxylationc	44 ± 13d	0.63 ± 0.08
	Ketone formatione	47 ± 11	0.20 ± 0.02
Yeast microsomes expressing:
human CYP1A1	Hydroxylation	< 10	1.14 ± 0.12
	Ketone formation	nt	0.63 ± 0.06d*
human CYP1A2	Hydroxylation	50 ± 21	0.18 ± 0.04
	Ketone formation	nt	nd
human CYP2C8	Hydroxylation	1450fg (Hill: 1.3)	1.03g ± 0.26
	Ketone formation	nt	nd
> human CYP2C9	Hydroxylation	55 ± 19	0.13 ± 0.02
	Ketone formation	nt	nd
human CYP3A4	Hydroxylation	282g ± 61	0.29g ± 0.03
	Ketone formation	nt	0.04 ± 0.002d*

^aExcept for ketone formation by the expressed enzymes, where the data correspond to v at 200 µ m rac-RPR 127025

^bthis pool of microsomes contained 0.37 nmol P450 mg⁻¹ protein

^c8-hydroxylation of CMV423

^dstandard errors from the fit of the data, except

^d*s.d. of duplicates

^eincubation of rac-RPR 127025

^fS₅₀ value

^gestimated, because a high concentration of DMSO (1.9%) had to be used; nt = not tested

nd = metabolite not detected, even at a substrate concentration of 200 µ m.