The role of CYP3A5 polymorphism and dose adjustments following conversion of twice-daily to once-daily tacrolimus in renal transplant recipients. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Zaltzman, Alina; Glick, Lauren; Zaltzman, Jeffrey; Nash, Michelle; Huang, Michael; Prasad, G.
• Is Part Of: Transplantation research. Volume 5:Issue 1(2016)
• Page Start: 1
• Page End: 6
• Publication Date: 2016-12
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.954
• DOI: 10.1186/s13737-016-0031-6
• Languages: English
• ISSNs: 2047-1440

Abstract

Abstract Background Tacrolimus is available as twice-daily Prograf® (Tac-BID) and the once-daily formulation, Advagraf® (Tac-OD). Although therapeutically equivalent, some transplant recipients require dose adjustments to achieve similar tacrolimus trough concentrations [Tac C0 ] after conversion between formulations. Tacrolimus is primarily metabolized by cytochromeP450 3A5 (CYP3A5 ). We sought to determine whether genetic polymorphisms in theCYP3A5 enzyme;CYP3A5 *1/*1 andCYP3A5 *1/*3 (expressers) compared toCYP3A5 *3/*3 (non-expressers) could account for discrepancies in dose requirements following conversion from Tac-BID to Tac-OD. Methods A cohort of 60 renal transplant recipients (RTR) from our larger conversion study of 496 patients underwent additional testing forCY3A5 genetic polymorphisms. Analysis included demographics, tac dosing and [Tac C0 ] pre- and post-conversion and dosing changes relative toCYP3A5 genotypes.CYP3A5 genetic polymorphisms were identified through analysis of genomic DNA. Results Conversion from tac bid to tac OD in this cohort required a mean (SD) dose increase from 3.1 (1.0) mg/day to 3.8 (1.3) mg/day (p = 0.007), to achieve similar [Tac C0 ]. The *1/*3 expresser group required a greater percentage dose adjustment (56.7 %) in converting from Tac-BID to Tac-OD as compared to the *3/*3 non-expresser group (26.6 %). Similar findings were observed with the both expresser groups combined (*1/*1 &*1/*3). The expressers were significantly more highly represented in the East Asian cohort. Conclusions TheCYP3A5 expresser polymorphism necessitates an increase in dosing upon conversion from Tac-BID to Tac-OD, with the expresser genotypes contributing significantly to this finding. Given the variability in frequency ofCYP3A5 genotypes in various ethnic groups, future studies should account for both isoenzyme polymorphism and ethnicity in optimizing dosing requirements. Trial registration Clinical trials.gov identifier:NCT01884480