Metabolic pathways of 4-[(3-methoxyphenyl)methyl]-2,2,6,6-tetramethyl-1-oxa-4-aza-2,6- disilacyclohexane (MPSC) hydrochloride, a silicon-containing xenobiotic, in rat, dog, and man.
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.
Dain
J G
JG
Sandoz Research Institute, Sandoz Pharmaceuticals Corporation, E. Hanover, NJ 07936, USA.
Nicoletti
J
J
D000818:Animals; D001593:Benzyl Compounds / Q000493:pharmacokinetics* / Q000652:urine; D004285:Dogs; D006801:Humans; D009125:Muscle Relaxants, Central / Q000493:pharmacokinetics; D017646:Organosilicon Compounds / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D012825:Silicon; D013045:Species Specificity; D015262:Xenobiotics / Q000493:pharmacokinetics*
D001593:Benzyl Compounds; D009125:Muscle Relaxants, Central; D017646:Organosilicon Compounds; D015262:Xenobiotics; C040982:4-((3-methoxyphenyl)methyl)-2,2,6,6-tetramethyl-1-oxa-4-aza-2,6-disilacyclohexane; D012825:Silicon