INHIBITION OF THE HEPATIC-UPTAKE OF PARACETAMOL SULFATE BY ANIONIC COMPOUNDS

The effect of anionic compounds on the hepatic uptake of paracetamol s ulphate, a conjugative metabolite of paracetamol, has been studied. He patic uptake of paracetamol sulphate by isolated hepatocytes was inhib ited by bromosulphophthalein, dibromosulphophthalein and p-nitrophenyl sulphate, but not by probenecid or cholic acid. Bromosulphophthalein and dibromosulphophthalein also inhibited the uptake of paracetamol su lphate in the rat isolated perfused liver. Saturable uptake of paracet amol sulphate was also observed in the absence of inorganic sulphate. The uptake of paracetamol sulphate was reduced by 1 and 10 mM inorgani c sulphate. Bromosulphophthalein and p-nitrophenyl sulphate inhibited the uptake of paracetamol sulphate in the absence of inorganic sulphat e. These results indicate that paracetamol sulphate shares a transport er with bromosulphophthalein, dibromosulphophthalein and p-nitrophenyl sulphate, all of which contain the sulphate or sulphonate group. Ther efore, the sulphate or sulphonate moiety might be crucial for interact ion with the transporter, and mutual inhibition of hepatic uptake amon g these compounds is likely.