Inhibition of the hepatic uptake of paracetamol sulphate by anionic compounds.
The effect of anionic compounds on the hepatic uptake of paracetamol sulphate, a conjugative metabolite of paracetamol, has been studied. Hepatic uptake of paracetamol sulphate by isolated hepatocytes was inhibited by bromosulphophthalein, dibromosulphophthalein and p-nitrophenyl sulphate, but not by probenecid or cholic acid. Bromosulphophthalein and dibromosulphophthalein also inhibited the uptake of paracetamol sulphate in the rat isolated perfused liver. Saturable uptake of paracetamol sulphate was also observed in the absence of inorganic sulphate. The uptake of paracetamol sulphate was reduced by 1 and 10 mM inorganic sulphate. Bromosulphophthalein and p-nitrophenyl sulphate inhibited the uptake of paracetamol sulphate in the absence of inorganic sulphate. These results indicate that paracetamol sulphate shares a transporter with bromosulphophthalein, dibromosulphophthalein and p-nitrophenyl sulphate, all of which contain the sulphate or sulphonate group. Therefore, the sulphate or sulphonate moiety might be crucial for interaction with the transporter, and mutual inhibition of hepatic uptake among these compounds is likely.
Sakuma-Sawada
N
N
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Iida
S
S
Mizuma
T
T
Hayashi
M
M
Awazu
S
S
D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D000838:Anions; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D004347:Drug Interactions; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D010477:Perfusion; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000494:pharmacology; D013448:Sulfobromophthalein / Q000494:pharmacology; D014528:Uricosuric Agents / Q000494:pharmacology
D000838:Anions; D002793:Cholic Acids; D004396:Coloring Agents; D009578:Nitrobenzenes; D013431:Sulfates; D014528:Uricosuric Agents; D013448:Sulfobromophthalein; C023379:4-nitrophenyl sulfate; C012479:dibromosulphthalein; D000082:Acetaminophen; D019826:Cholic Acid; D011339:Probenecid; C045667:acetaminophen sulfate ester