Correlation between rates of saquinavir metabolite formation in human small-intestinal microsomes
Correlation (r2)* | |||||||
---|---|---|---|---|---|---|---|
M-1 | M-2 | M-3 | M-4 | M-5 | M-6 | M-7 | |
M-1 | 0.88 | 0.78 | 0.88 | 0.80 | 0.70 | 0.85 | |
M-2 | 0.90 | 0.99 | 0.97 | 0.91 | 0.99 | ||
M-3 | 0.87 | 0.88 | 0.92 | 0.86 | |||
M-4 | 0.98 | 0.86 | 0.96 | ||||
M-5 | 0.89 | 0.94 | |||||
M-6 | 0.91 |
The rates of saquinavir metabolite formation were assessed with small-intestinal microsomes from 17 individual donors. Human small-intestinal microsomes were diluted with reaction buffer to give a final protein concentration of ∼0.05 mg/ml. Microsomes were warmed at 37°C in the presence of a NADPH-generating system for 3 min, and reactions were initiated by the addition of 10 μl of a 0.5 mM saquinavir solution in 1:1 acetonitrile:water to 0.99 ml reaction mixture. Reactions were terminated after 15 min by the addition of 1 ml of acetonitrile.
* Correlations between saquinavir metabolites were statistically significant, p < 0.001.