Effects of routes, concentrations and genetic polymorphisms on posaconazole–tacrolimus interactions in allogeneic haematopoietic cell transplantation
There is no prospective research on factors influencing posaconazole (PSCZ)-tacrolimus (TAC) interactions. This prospective observational study analysed 30 allogeneic haematopoietic cell transplantation recipients: 19 started PSCZ while receiving oral (n = 10) or intravenous (IV) TAC (n = 9) and 11 switched from IV to oral TAC during PSCZ administration. Following PSCZ initiation, the median TAC dose reductions were 45% for oral and 39% for IV TAC. Oral TAC concentration-to-dose ratios (C/D) significantly increased over 2 weeks (P < .01) and correlated with PSCZ concentrations (ρ = 0.92, P < .01), whereas IV TAC C/D showed no significant changes or correlations. The median IV to oral TAC conversion ratio was 2.86. Linear regression analyses revealed significant associations between PSCZ concentrations and oral TAC C/D changes, CYP3A5 polymorphisms and IV TAC C/D changes, and CYP3A5 polymorphisms and TAC conversion ratios. TAC route, PSCZ concentrations and genetic polymorphisms may influence PSCZ-TAC interactions.
Authors
- Masatomo Kuno (ORCID: https://orcid.org/0000-0003-4548-147X)
- Mika Nakamae (ORCID: https://orcid.org/0000-0002-9200-4804)
- Hiroyuki Yasui (ORCID: https://orcid.org/0000-0003-3317-3947)
- Masayuki Hino
- Kentaro Ido (ORCID: https://orcid.org/0000-0003-1253-6948)
- Yasuhiro Nakashima (ORCID: https://orcid.org/0000-0003-3025-723X)
- Yusuke Okayama (ORCID: https://orcid.org/0000-0003-3435-8951)
- Yosuke Nakaya (ORCID: https://orcid.org/0000-0003-3337-1599)
- Hiroshi Kakeya (ORCID: https://orcid.org/0000-0002-6251-1696)
- Kazuki Sakatoku (ORCID: https://orcid.org/0000-0002-2206-8693)
- Wataru Shibata (ORCID: https://orcid.org/0000-0003-0326-6659)
- Makoto Moriguchi
- Hiroshi Okamura
- Hirohisa Nakamae (ORCID: https://orcid.org/0000-0003-4203-990X)
- Mitsutaka Nishimoto (ORCID: https://orcid.org/0000-0002-0388-3836)
- Yosuke Makuuchi (ORCID: https://orcid.org/0000-0002-5230-6904)
- Joji Nagasaki (ORCID: https://orcid.org/0000-0003-0945-5469)
- Yukako Yasui
- Mirei Horiuchi
- Hideo Miyagawa
Institutions
- Kyoto Pharmaceutical University (JP)
- Osaka City University (JP)
- Sakai Municipal Hospital (JP)
- Daiyukai General Hospital (JP)
- Osaka Metropolitan University (JP)
- Tokyo Metropolitan University (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- British Journal of Clinical Pharmacology
- Published
- 2025-09-03
- DOI
- https://doi.org/10.1002/bcp.70264
- Primary Topic
- Antifungal resistance and susceptibility
- Type
- article
- Field-Weighted Citation Impact
- 0.00