Involvement of multidrug resistance-associated protein 2 (ABCC2/Mrp2) in biliary excretion of micafungin in rats.
The drug transporter, multidrug resistance-associated protein 2 (ABCC2/Mrp2), is known to play important roles in excretion of various drugs. In the present study, we investigated whether Mrp2 is involved in the transport of micafungin, a newly developed antifungal agent. When Sprague-Dawley rats received an intravenous injection of micafungin (1 mg/kg) in combination with cyclosporine, the cyclosporine significantly delayed the disappearance of micafungin from plasma and decreased the systemic clearance and volume of distribution at steady-state of micafungin to 54% and 65% of the corresponding control values, respectively. When Sprague-Dawley rats received a constant-rate infusion of micafungin, cyclosporine significantly decreased the steady-state biliary clearance of micafungin (approximately 80%). A significant decrease in the biliary clearance of micafungin (~60%) was observed in Eisai hyperbilirubinemic rats, which have a hereditary deficiency in Mrp2. The present findings at least suggest that Mrp2 is involved mainly in the hepatobiliary excretion of micafungin in rats.
Abe
Fumie
F
Department of Pharmacy and Pharmacokinetics, Aichi Medical University School of Medicine, Nagakute-cho, Aichi-gun, Aichi 480-1195, Japan.
Ueyama
Jun
J
Kimata
Akiko
A
Kato
Miki
M
Hayashi
Tamon
T
Nadai
Masayuki
M
Saito
Hiroko
H
Takeyama
Naoshi
N
Noguchi
Hiroshi
H
Hasegawa
Takaaki
T
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology; D054714:Echinocandins / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006932:Hyperbilirubinemia; D007275:Injections, Intravenous; D055666:Lipopeptides; D008074:Lipoproteins / Q000493:pharmacokinetics*; D008297:Male; D000077551:Micafungin; D051381:Rats; D017207:Rats, Sprague-Dawley
D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D000935:Antifungal Agents; D054714:Echinocandins; D004791:Enzyme Inhibitors; D055666:Lipopeptides; D008074:Lipoproteins; D016572:Cyclosporine; D000077551:Micafungin