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Tacrolimus has originally been registered as a twice-daily formulation (Prograf, Tac BID), although a once-daily formulation (Advagraf, Tac QD) is also available. A reduced intrapatient variability of Tac Cmin, a surrogate marker for 24-hour drug exposure (AUC0–24), has been suggested. The variability of AUC0–24 has never been studied prospectively yet. The purpose of this study was to investigate the change in intrapatient variability of Tac AUC0–24 after converting from Tac BID to Tac QD.Forty renal transplant patients on Tac BID were converted on a 1:1 (mg/mg) basis to Tac QD in an investigator-driven comparative pharmacokinetic (PK) study. AUC0–24 was determined five times before and after conversion. Duplicate samples were collected by the patients themselves using the dried blood spot method. The main outcome measure is the change in intrapatient variability of AUC0–24 expressed as coefficient of variation (CV). Moreover, the influence of Cyp3A5 genotype polymorphism on the change in CV was studied.In total, 400 AUC0–24 profiles were available for analysis. Conversion to Tac QD resulted in a significant improvement in intra-patient CV from 14.1% to 10.9% (P=0.012). Patients with the Cyp3A5*1/*3 genotype (n=11) had a numerically larger improvement in CV than patients with the CYP3A5*3/*3 genotype.Intrapatient CV of Tac AUC0–24 improved after converting from Tac BID to Tac QD in stable renal transplant patients, especially in patients with the CYP3A5*1/3 genotype. Given the very strict protocol of this PK study, this improvement is most likely due to the different intrinsic PK properties of Tac QD and Tac BID.