Drug interaction of (S)-warfarin, and not (R)-warfarin, with itraconazole in a hematopoietic stem cell transplant recipient

Autor: Masatomo Miura, Hiroyuki Tagawa, Naohito Fujishima, Hirobumi Saitoh, Kenichi Sawada, Syu-ichi Kanno, Mitsugu Itoh, Tomoko Yoshioka, Naoto Takahashi, Miho Nara, Makoto Hirokawa, Shoutaro Kato, Yoshihiro Kameoka
Rok vydání: 2011
Předmět:
Zdroj: Clinica Chimica Acta. 412:2002-2006
ISSN: 0009-8981
DOI: 10.1016/j.cca.2011.06.035
Popis: Background Itraconazole is a potent inhibitor of CYP3A4 and P-glycoprotein, but not CYP2C9. Herein, we report a case study in which the plasma concentration of the CYP2C9 substrate ( S )-warfarin, and not the CYP3A4 substrate ( R )-warfarin, increased with itraconazole coadministration. Case A 67-y-old man received an allogenic bone marrow transplant for acute lymphoid leukemia. He was taking oral itraconazole (200 mg/day) and was started on a warfarin dose of 2.0 mg/day. The plasma concentrations of ( S )- and ( R )-warfarin 3 days after starting warfarin administration were 216 and 556 ng/mL, respectively (INR 0.98), and after 10 days, the concentrations were 763 and 545 ng/mL, respectively (INR 2.43). On day 11 after withdrawal of itraconazole, the concentrations of ( S )- and ( R )-warfarin were 341 and 605 ng/mL, respectively (INR 1.38). The concentration of ( R )-warfarin was not affected by itraconazole; however, the final ( S )-warfarin concentration had increased 7.3-fold. The ( S )-warfarin/( S )-7-hydroxywarfarin ratio decreased to 2.45 from 8.40 after discontinuation of itraconazole. The permeability of warfarin enantiomers across Caco-2 cells was not influenced by itraconazole and showed no difference between enantiomers. Conclusions Careful INR monitoring is necessary for warfarin co-administration with itraconazole. Further examination is necessary to elucidate mechanisms of the interaction between warfarin and itraconazole.
Databáze: OpenAIRE
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