Metabolic pathways of 4-[(3-methoxyphenyl)methyl]- 2,2,6,6-tetramethyl-l-oxa-4-aza-2,6-disilacyclohexane (MPSC) hydrochloride, a silicon-containing xenobiotic, in rat, dog, and man

Abstract

1. The metabolic pathways of Sandoz compound 58–112, 4-[(3-methyoxyphenyl)-methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2,6-disilacyclohexane (MPSC) hydrochloride were evaluated in rat, dog, and man after a single oral dose.

2. In rat, dog and man the major route of elimination was renal. In the dog, renal excretion of unchanged MPSC represented a substantial portion of the dose whereas in rat and man MPSC was completely metabolized prior to excretion.

3. In rat and man, the major end-product metabolite was 3'-[{(hydroxydimethylsilyl)-methylamino}methyl]-phenol glucuronide; 4-[(3-hydroxyphenyl)-methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2,6-disilacyclohexane and 4-[(4-hydroxy-3-methoxyphenyl)-methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2,6-disilacyclohexane and their conjugates were also present. In dog, the major end-product metabolites were the hippurate of 3-methoxybenzoic acid and 3-hydroxybenzoic acid.