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장기 이식 환자에서 voriconazole과 cyclosporine 또는 tacrolmus의 상호작용

The interaction between voriconazole and cyclosporine or tacrolimus in organ transplant patients

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초록

In organ transplant patients, the opportunity of fungi infections such as invasive aspergillosis increase by use of immunosuppresant drugs and voriconazole is recommended as primary treatment drug. When voriconazole is administered with cyclosporine(CsA) or tacrolimus(FK506), caution about increment of blood CsA or FK506 concentrations that caused by the change of CYP3A4 activity is required but few domestic cases of interaction were reported yet. The purpose of this study was to assess the effect of voriconazole on the blood CsA or FK506 concentrations in transplant recipients and the factors of recipients that have an effect on the results. 25 transplant recipients who were administered voriconazole with CsA or FK506 from January 1 of 2006 to August 17 of 2008 in Asan Medical Center were objects (12 patients on CsA coadministration arm – 9 males, 3 females; 41~62years;2 liver, 2 kidney, 3 bone marrow, 5 heart transplant recipients, and 13 on FK506 coadministration arm – 7 males, 6 females;26~65years;10 liver, 2 kidney, 1 heart transplant recipients). Blood CsA or FK506 concentrations before and after coadministration of voriconazole, and maximum concentration in one month from the first day of coadministration were monitored retrospectively. In most cases CsA or FK506 were administered as recommended doses regardless of coadministration of voriconazole, and blood concentration increased from 239.42±126.77ng/ml to maximum 411.92±225.76ng/ml in CsA coadministration arm(p=0.003), and from 7.72±2.79ng/ml to maximum 19.16±9.35ng/ml in FK506 coadministration arm(p=0.003). Gender, age, and the kind of transplant organ did not affect to the change of blood concentration in both two arms. In consequences, administration of voriconazole could affect on the blood CsA or FK506 concentration, and in cases of administration of voriconazole in transplant recipients treated with CsA or FK506, close monitoring and dose adjustment is needed.

Abstract

In organ transplant patients, the opportunity of fungi infections such as invasive aspergillosis increase by use of immunosuppresant drugs and voriconazole is recommended as primary treatment drug. When voriconazole is administered with cyclosporine(CsA) or tacrolimus(FK506), caution about increment of blood CsA or FK506 concentrations that caused by the change of CYP3A4 activity is required but few domestic cases of interaction were reported yet. The purpose of this study was to assess the effect of voriconazole on the blood CsA or FK506 concentrations in transplant recipients and the factors of recipients that have an effect on the results. 25 transplant recipients who were administered voriconazole with CsA or FK506 from January 1 of 2006 to August 17 of 2008 in Asan Medical Center were objects (12 patients on CsA coadministration arm – 9 males, 3 females; 41~62years;2 liver, 2 kidney, 3 bone marrow, 5 heart transplant recipients, and 13 on FK506 coadministration arm – 7 males, 6 females;26~65years;10 liver, 2 kidney, 1 heart transplant recipients). Blood CsA or FK506 concentrations before and after coadministration of voriconazole, and maximum concentration in one month from the first day of coadministration were monitored retrospectively. In most cases CsA or FK506 were administered as recommended doses regardless of coadministration of voriconazole, and blood concentration increased from 239.42±126.77ng/ml to maximum 411.92±225.76ng/ml in CsA coadministration arm(p=0.003), and from 7.72±2.79ng/ml to maximum 19.16±9.35ng/ml in FK506 coadministration arm(p=0.003). Gender, age, and the kind of transplant organ did not affect to the change of blood concentration in both two arms. In consequences, administration of voriconazole could affect on the blood CsA or FK506 concentration, and in cases of administration of voriconazole in transplant recipients treated with CsA or FK506, close monitoring and dose adjustment is needed.

참고문헌 (6)

  1. Nikie D. Greer, "Voriconazole: the newest t ri azo le antifungal agent", Baylor University Medical Cen ter Proceedings, 16, pp.241~248 (2003)
  2. Raoul Herbrecht, "for the Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer and the Global Aspergillus Study Group : Voriconazole versus Amphotericin B for Primary Therapy of Invasive Aspergillosis", The New England Journal of Medicine, 347, pp.408~415 (2002)
  3. 장미수, "면역저하환자에서 진균의 기회감염", Hanyang medical reviews, 26, pp.25~33 (2006)
  4. Raman Venkataramanan, "Voriconazole Inhibition of the Metabolism of Tacrolimus in a Liver Transplant Recipient and in Human Liver Microsomes", Antimicrobial Agent and Chemotherapy, 46, pp.3091~3093 (2002)
  5. David W. Denning, "Efficacy and Safety of Voriconazole in the Treatment of Acute Invasive Aspergillosis", Clinical Infectious Diseases, 34, pp.563~571 (2002)
  6. 한국화이자제왜쥐, "브이펜드(보리코나졸) DC 자료집 주사제, 정제", ~

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