Table 2

Correlation between rate of formation of saquinavir metabolites with cytochrome P450 marker activities

Marker Enzyme Activity	CYP	Correlation (r²)
Marker Enzyme Activity	CYP	M-1	M-2	M-3	M-7
EthoxyresorufinO-dealkylation	1A2	0.03	0.08	0.05	0.11
CaffeineN3-demethylation	1A2	0.02	0.09	0.05	0.11
Coumarin 7-hydroxylation	2A	0.40^**	0.36^**	0.37^**	0.37^**
Tolbutamide methylhydroxylation	2C9	0.61^**	0.48^**	0.56^**	0.52^**
S-Mephenytoin 4-hydroxylation	2C19	0.28	0.18	0.23	0.22
DextromethorphanO-demethylation	2D6	0.00	0.00	0.00	0.00
Chlorzoxazone 6-hydroxylation	2E1	0.06	0.03	0.04	0.03
Testosterone 6β-hydroxylation	3A4	0.84^*	0.92^*	0.89^*	0.87^*
Lauric acid 12-hydroxylation	4A1	0.51^**	0.38^**	0.46^**	0.41^**

Saquinavir oxidation was assessed with Human Biologics, Inc., test kit that contained microsomes from 10 human livers and from one pooled liver. Human hepatic microsomes (0.2 mg/ml) were preincubated at 37°C for 3 min in the presence of a NADPH-generating system. Reactions were started by the addition of 10 μl of a 0.5 mM saquinavir solution in 1:1 acetonitrile:water to 0.99 ml reaction buffer, and reactions were terminated after 5 min by the addition of 1 ml of acetonitrile.
* Statistically significant p < 0.001.
** Statistically significant p < 0.05.