Immune outcomes of lung transplant recipients with different cytochrome P450 3A5 phenotypes after discontinuation of voriconazole antifungal prophylaxis.
Clin Transplant
; 38(1): e15235, 2024 01.
Article
in En
| MEDLINE
| ID: mdl-38289893
ABSTRACT
INTRODUCTION:
Tacrolimus forms the backbone of immunosuppression regimens in lung transplant recipients (LTRs). It is extensively metabolized by cytochrome P450 (CYP) 3A5 enzymes, of which polymorphisms can significantly affect tacrolimus dose requirements. It is unknown how coadministration of tacrolimus with voriconazole, a potent CYP3A5 inhibitor, affects rejection rates or empiric dose adjustments needed after voriconazole discontinuation.METHODS:
This retrospective cohort study compares LTRs with poor (PR) versus intermediate/extensive (IE) CYP3A5 metabolizer phenotypes. The primary endpoint is cumulative immune outcomes within three months of voriconazole discontinuation; secondary endpoints include change in tacrolimus dose-to-concentration ratios after voriconazole discontinuation.RESULTS:
Thirty-four patients underwent fullanalysis:
13 IE and 21 PR metabolizers. A higher proportion of IE metabolizers were African American (46.2% vs. 9.5%, p = .03). There was no significant difference in composite immune outcomes, though there was a proportionally higher frequency of new donor-specific antibody development in PR metabolizers (14.3% vs 7.7%, p = .56). Both groups required approximately 2.5 to 3-fold tacrolimus dose increases post-voriconazole discontinuation to re-attain therapeutic levels.CONCLUSION:
This novel investigation sheds light on how CYP3A5 phenotype could be used to guide tacrolimus dosing, with the goal of preventing both toxicity and organ rejection.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tacrolimus
/
Immunosuppressive Agents
Type of study:
Observational_studies
Limits:
Humans
Language:
En
Journal:
Clin Transplant
Journal subject:
TRANSPLANTE
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Dinamarca