Metabolization of 14C-N-acetylpenicillamine and 14C-cysteine in relation to 1-chloro-2,4-dinitrobenzene and sulphobromophtalein conjugation and biliary excretion in the rat.

Upon intraperitoneal administration of N-(1-14C)-acetylpenicillamine (NAPA) to rats, at a dose of 1-2 mmol/kg body weight, a 14C-labelled metabolite of NAPA together with unchanged NAPA were excreted in bile. The NAPA metabolite was characterized by acid hydrolysis and thin-layer chromatography. Rats previously depleted of liver glutathione by intraperitoneal injection of cyclohexene oxide, 2.5 mmol/kg body weight, were given intraperitoneal injections of 14C-cysteine, 0.5 mmol/kg, or 14C-NAPA, 1-2 mmol/kg, together with 1-chloro-2,4-dinitrobenzene (DNB), 1 mmol/kg, or bromosulphophtalein (BSP), 0.5 mmol/kg body weight. Simultaneous administration of 14C-cysteine and DNB or BSP lead to rapid incorporation of 14C-activity in glutathione and glutathione conjugates of DNB and BSP being excreted in bile. Upon simultaneous administration of 14C-NAPA and DNB or BSP, 14C-labelled metabolite of NAPA not conjugated to DNB or BSP, and unchanged NAPA, together with non-labelled glutathione conjugates of DNB or BSP, were excreted in bile. This is interpreted as indicating that neither NAPA nor NAPA metabolite are capable of forming conjugates of DNB or BSP in rat liver.