Metabolism and disposition studies with a [35S]-labelled growth promotor: bis(N1-methyl-N2-methylsulphonyl) guanidinylethyl] disulphide.
The disposition and metabolism of the [35S]-labelled growth promotor bis[N1-methyl- N2-methylsulphonyl) guanidinylethyl] disulphide was studied in the rat following oral administration. There was rapid and significant absorption of drug-derived products evidenced by maximum concentrations for plasma and the majority of sampled tissues at 1 h post dose, and extensive renal clearance, with greater than 62% of dose voided in urine in 12 h. Analysis of urine revealed that the administered compound had been completely metabolised to five metabolites of which the two major products have been characterised. A metabolic pathway involving reductive cleavage of the disulphide bond, followed by S-methylation and sulphoxidation would appear to be involved in the biotransformation of the compound.
Facchini
V
V
Biopharmaceutical Research, Rhone-Poulenc Ltd., Dagenham Essex, U.K.
Jones
M
M
Smith
G E
GE
D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D006133:Growth Substances / Q000493:pharmacokinetics* / Q000652:urine; D006146:Guanidines / Q000493:pharmacokinetics* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013055:Spectrophotometry, Infrared; D013462:Sulfur Radioisotopes
D006133:Growth Substances; D006146:Guanidines; D013462:Sulfur Radioisotopes; C063824:bis((N(1)-methyl-N(2)-methylsulfonyl)guanidinylethyl)disulfide