PURPOSE: The purpose of this study was to investigate the interactions of itraconazole (ITCZ) with orally administered calcineurin inhibitors (CNIs) in Japanese allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: Sixteen HSCT patients (8 patients each receiving tacrolimus or cyclosporine) were enrolled. An ITCZ oral solution was administered from day 30 after the initiation of ITCZ administration as a loading dose. Before the co-administration of ITCZ and CNI and 1 week daily thereafter, whole blood ITCZ and CNI (tacrolimus or cyclosporine) concentrations were measured in samples taken just before (C0h) and 2 h (C2h) after CNI administration. RESULTS: The median dose-adjusted C0h values of tacrolimus and cyclosporine on day 7 after the start of ITCZ co-administration were 5.6- and 2.7-fold higher, respectively, than the corresponding values obtained before the initiation of ITCZ treatment. On day 7 after ITCZ treatment, the mean single dosages of tacrolimus and cyclosporine were reduced to 33.7 and 66.5 % of the dosages before ITCZ co-administration, respectively, to adjust the CNI target concentration. Although ITCZ co-administration did not alter the dose-adjusted C0h values of tacrolimus in a patient with a CYP3A5 1/ 1 allele, it did change this value of tacrolimus in patients with CYP3A5 3 alleles. However, in patients receiving cyclosporine, no such tendency was observed. CONCLUSION: The magnitude of the interaction between orally administered tacrolimus and ITCZ was significantly greater than that between cyclosporine and ITCZ. Prospective analysis of the CYP3A5 polymorphism may be important to ensure safe and reliable immunosuppressive therapy with tacrolimus in patients treated with ITCZ.
PURPOSE: The purpose of this study was to investigate the interactions of itraconazole (ITCZ) with orally administered calcineurin inhibitors (CNIs) in Japanese allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: Sixteen HSCT patients (8 patients each receiving tacrolimus or cyclosporine) were enrolled. An ITCZ oral solution was administered from day 30 after the initiation of ITCZ administration as a loading dose. Before the co-administration of ITCZ and CNI and 1 week daily thereafter, whole blood ITCZ and CNI (tacrolimus or cyclosporine) concentrations were measured in samples taken just before (C0h) and 2 h (C2h) after CNI administration. RESULTS: The median dose-adjusted C0h values of tacrolimus and cyclosporine on day 7 after the start of ITCZ co-administration were 5.6- and 2.7-fold higher, respectively, than the corresponding values obtained before the initiation of ITCZ treatment. On day 7 after ITCZ treatment, the mean single dosages of tacrolimus and cyclosporine were reduced to 33.7 and 66.5 % of the dosages before ITCZ co-administration, respectively, to adjust the CNI target concentration. Although ITCZ co-administration did not alter the dose-adjusted C0h values of tacrolimus in a patient with a CYP3A5 1/ 1 allele, it did change this value of tacrolimus in patients with CYP3A5 3 alleles. However, in patients receiving cyclosporine, no such tendency was observed. CONCLUSION: The magnitude of the interaction between orally administered tacrolimus and ITCZ was significantly greater than that between cyclosporine and ITCZ. Prospective analysis of the CYP3A5 polymorphism may be important to ensure safe and reliable immunosuppressive therapy with tacrolimus in patients treated with ITCZ.
Authors: Pierre Wallemacq; Gregory T Maine; Keith Berg; Thomas Rosiere; Pierre Marquet; Giuseppe Aimo; Giulio Mengozzi; Julianna Young; Kurt Wonigeit; Robert Kretschmer; Bendicht Wermuth; Rainer W Schmid Journal: Ther Drug Monit Date: 2010-04 Impact factor: 3.681
Authors: E Hustert; M Haberl; O Burk; R Wolbold; Y Q He; K Klein; A C Nuessler; P Neuhaus; J Klattig; R Eiselt; I Koch; A Zibat; J Brockmöller; J R Halpert; U M Zanger; L Wojnowski Journal: Pharmacogenetics Date: 2001-12
Authors: Nina Isoherranen; Kent L Kunze; Kyle E Allen; Wendel L Nelson; Kenneth E Thummel Journal: Drug Metab Dispos Date: 2004-07-08 Impact factor: 3.922
Authors: I E Templeton; K E Thummel; E D Kharasch; K L Kunze; C Hoffer; W L Nelson; N Isoherranen Journal: Clin Pharmacol Ther Date: 2007-05-09 Impact factor: 6.875
Authors: P Badri; S Dutta; E Coakley; D Cohen; B Ding; T Podsadecki; B Bernstein; W Awni; R Menon Journal: Am J Transplant Date: 2015-02-23 Impact factor: 8.086
Authors: Camila Sinkos; Thais Gagno Grillo; Ana Clara Muraro Bonini; Lucas Gonçalves Cardoso; Erika Mayumi Watanabe; Ricardo de Souza Cavalcante; Giovanni Faria Silva; Fabio da Silva Yamashiro; Fernando Gomes Romeiro; Talles Bazeia Lima Journal: Med Mycol Case Rep Date: 2021-02-23