ボリコナゾール薬物動態が投与中止後のリファンピシンに影響を受けた一症例

Abstract

The purposes of this study were to demonstrate how the interaction between rifampicin and voriconazole can be managed clinically and to characterize the changes in voriconazole concentration levels after discontinuation of rifampicin.The concomitant administration of voriconazole and rifampicin is contraindicated because the interaction between these drugs results in a subtherapeutic concentration of voriconazole.In this regard,voriconazole is known to be metabolized by CYP2C19,2C9,3A4,and rifampicin is a potent inducer of CYP3A4.The interaction between rifampicin and voriconazole was investigated in a 70 year old male patient with severe infection in a prosthetic graft,necessitating simultaneous treatment with vancomycin and rifampicin.Rifampicin therapy was discontinued to start antifungal treatment with voriconazole.Interaction between the 2 drugs was evaluated by measuring voriconazole trough levels 4,7,11,18,and 29 days after starting therapy with it,performing the assays by high-performance liquid chromatography.Four days after starting voriconazole,we observed a significant decrease in its serum concentration,to 0.24μg/mL.After 7 days,it had increased to 0.84μg/mL and to 1.24μg/mL after 11 days,and thereafter,continued to gradually increase.Thus,after discontinuing rifampicin,CYP induction continued to be strong for the first 11 days and then became more moderate over the course of a month.In conclusion,it is essential that patients being treated with both rifampicin and voriconazole have their voriconazole concentrations monitored when rifampicin therapy is discontinued.