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We aimed to describe the relationship between tacrolimus whole blood and PBMC concentrations, and the influence of patient characteristics on this relationship by developing a population pharmacokinetic model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We prospectively enrolled 63 stable adult kidney\u2010transplanted patients and collected dense (12\u2010h, n\u2009=\u200918) or sparse (4\u2010h, n\u2009=\u200945) pharmacokinetic profiles of tacrolimus. PBMCs were isolated from whole blood (Ficoll density gradient centrifugation), and drug concentrations in whole blood and PBMCs were analysed using liquid chromatography\u2010mass spectrometry. Patient genotype (<jats:italic>CYP3A4\/5<\/jats:italic>, <jats:italic>ABCB1, NR1I2<\/jats:italic>) was assessed with PCR. Population pharmacokinetic modelling and statistical evaluation was performed using NONMEM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tacrolimus whole blood concentrations were well described using a two\u2010compartment pharmacokinetic model with a lag\u2010time and first\u2010order absorption and elimination. Tacrolimus PBMC concentrations were best estimated from whole blood concentrations with the use of a scaling factor, the ratio of whole blood to PBMC concentrations (<jats:italic>R<\/jats:italic><jats:sub>C:PBMC<\/jats:sub>), which was the extent of tacrolimus distribution into PBMC. <jats:italic>CYP3A5*1<\/jats:italic> non\u2010expressors and <jats:italic>NR1I2\u201025\u2009385T<\/jats:italic> allele expressors demonstrated higher <jats:italic>R<\/jats:italic><jats:sub>C:PBMC<\/jats:sub> ratios of 42.4% and 60.7%, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tacrolimus PBMC concentration could not be accurately predicted from whole blood concentrations and covariates because of significant residual unexplained variability in the distribution of tacrolimus into PBMCs and may need to be measured directly if required for future 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