Pharmacokinetic study of the hepatobiliary transport of indomethacin.

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Kouzuki H, Suzuki H, Sugiyama Y

Pharmacokinetic study of the hepatobiliary transport of indomethacin.

Pharm Res. 2000 Apr;17(4):432-8.

PubMed ID

10870987 [ View in PubMed

]

Abstract

PURPOSE: The biliary excreted amount of indomethacin and its glucuronide is related to the intestinal toxicity of this drug. In the present study, we investigated the hepatobiliary transport of indomethacin. METHODS: The uptake of indomethacin into primary cultured rat hepatocytes and COS-7 cells transfected with cDNA encoding sodium taurocholate co-transporting polypeptide or organic anion transporting polypeptide 1 was examined. Moreover, we compared the biliary excretion of indomethacin and its glucuronide between Sprague-Dawley (SD) rats and Eisai hyperbilirubinemic rats (EHBR) whose canalicular multispecific organic anion transporter/multidrug resistance associated protein 2 (cMOAT/MRP2) function is hereditarily defective. RESULTS: The uptake of indomethacin into rat hepatocytes was mediated by Na+-dependent and independent active transport systems. Neither transfectant stimulated the uptake of indomethacin. After intravenous infusion of indomethacin to SD rats, the biliary excretion of indomethacin glucuronide exceeded that of indomethacin. The indomethacin transport clearance across the bile canalicular membrane was comparable between SD rats and EHBR, whereas the corresponding value for indomethacin glucuronide in EHBR was approximately 50% that in SD rats. CONCLUSIONS: These results indicate that another transporter(s) is involved in the hepatic uptake of indomethacin and the canalicular transport of indomethacin glucuronide is mediated by cMOAT/MRP2 whereas that of indomethacin is not mediated by cMOAT/MRP2.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Indomethacin	Canalicular multispecific organic anion transporter 1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Indomethacin	Sodium/bile acid cotransporter	Protein	Humans	Unknown	Substrate	Details
Indomethacin	Solute carrier organic anion transporter family member 1A2	Protein	Humans	Unknown	Substrate Inhibitor	Details