Comparison of 12-hydroxy and 39-O-desmethyl sirolimus formation by microsomes isolated from the proximal small intestine of different species
| Species | Metabolite formation rate | 12-Hydroxy sirolimus | 39-O-Desmethyl sirolimus |
|---|---|---|---|
| pmol·min−1·mg−1 protein | μM | ||
| Rat (n = 5) | 32.1 ± 13.8 | 0.34 ± 0.09 | 0.18 ± 0.05 |
| Dog (n = 3) | 73.9 ± 29.5 | 0.76 ± 0.34 | 0.28 ± 0.09 |
| Pig (n = 10) | 77.2 ± 34.7 | 0.97 ± 0.43 | 0.32 ± 0.10 |
| Human (n = 14) | 97.7 ± 61.3 | 1.12 ± 0.36 | 0.54 ± 0.13 |
Sirolimus at a final concentration of 10 μM was incubated with small intestinal microsomes isolated from the rat, dog, pig and human duodenum. The formation rate of all sirolimus metabolites measured by HPLC and the final concentrations of the major metabolites after 20-min incubation are given as mean ± S.D.