PT  - JOURNAL ARTICLE
AU  - Christians, U
AU  - Sattler, M
AU  - Schiebel, H M
AU  - Kruse, C
AU  - Radeke, H H
AU  - Linck, A
AU  - Sewing, K F
TI  - Isolation of two immunosuppressive metabolites after in vitro metabolism of rapamycin.
DP  - 1992 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 186--191
VI  - 20
IP  - 2
4099  - http://dmd.aspetjournals.org/content/20/2/186.short
4100  - http://dmd.aspetjournals.org/content/20/2/186.full
SO  - Drug Metab Dispos1992 Mar 01; 20
AB  - Rapamycin was incubated with human liver microsomes and an NADPH regenerating system, the metabolites were purified by semipreparative HPLC, and their structures were elucidated by direct chemical ionization and FAB-MS. At least six fractions were isolated containing rapamycin metabolites, indicating that rapamycin is metabolized by the human liver cytochrome P-450 system. One of these metabolites was identified as 41-O-demethyl-rapamycin. A second metabolite was hydroxylated in a yet unknown position. These two metabolites retained immunosuppressive activity in a phytohemagglutinin-stimulated human lymphocyte assay with IC50S of 1 and 1.5 nmol/liter, respectively. Rapamycin was metabolized by rat small intestinal microsomes to at least two metabolites, indicating extra-hepatic metabolism of rapamycin.