IntroductionIntrapatient variability (IPV) of tacrolimus and its predictors post-lung transplant are unclear. Project AimsThis program evaluation aimed to characterize the IPV of immediate-release versus LCP-tacrolimus and predictors of variability ≥30% in lung transplant recipients. DesignAdult lung transplant recipients who received immediate-release- or LCP-tacrolimus from January 2016 through August 2023 were included in this single-center retrospective evaluation. Immediate-release- and LCP-tacrolimus groups were matched 2:1 by time from transplant, presence of azole antifungal, and ethnicity. Three previously published equations calculated IPV. Outcomes to determine clinical impact of tacrolimus variability included de novo donor-specific antibody (DSA) development, rejection, graft loss/mortality, eGFR <60 mL/min, infection. Time in therapeutic range was assessed. Data were analyzed to determine predictors of variability ≥30%. ResultsThere were no significant differences in the variability of immediate-release- versus LCP-tacrolimus among 3 equations used. There was no difference in de novo DSA development, rejection, graft loss, mortality, eGFR <60 mL/min, or infection between groups. Recipients with rejection during follow-up had higher variability compared to those who did not (P = .04). Presence of CYP34A inhibition predicted variability >30% in multivariate analysis. Immediate-release tacrolimus had higher time in therapeutic range versus LCP-tacrolimus, 67% versus 33%, (P = .15). ConclusionThe IPV and associated clinical outcomes of immediate-release versus LCP-tacrolimus in lung transplant recipients did not significantly differ. Development of acute cellular rejection within 1 year follow-up was associated with higher tacrolimus variability regardless of formulation.
Keywords: clinical outcomes; descriptive; descriptive comparative; infection; pharmacokinetics; pharmacology; quantitative methods; rejection outcomes; research; statistics.