Evidence map›Paper›PMID 42477302›Full record

ReviewClinical pharmacokinetics2026

A Review of Population Pharmacokinetic Models and Dosing Algorithms Assessing the Influence of CYP3A5 Genotype and Other Clinical Covariates on Tacrolimus Pharmacokinetics.

Riley M Randolph, Sara Jubas, Li Gong, Raman Venkataramanan, Dhrita Khatri, Pamala A Jacobson, David Metz, Daniel J Crona

Abstract readReview
PubMed Publisher
In one paragraph

Review in Clinical pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Riley M Randolph *Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, 120 Mason Farm Road, CB 7361, Genetic Medicine Building 2090, Chapel Hill, NC, 27599, USA.ORCID http://orcid.org/0009-0005-8771-1191
Sara Jubas *Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, 120 Mason Farm Road, CB 7361, Genetic Medicine Building 2090, Chapel Hill, NC, 27599, USA.ORCID http://orcid.org/0009-0005-9546-4768
Li GongDepartment of Biomedical Data Science, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1739-8233
Raman VenkataramananDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-1893-3290
Dhrita KhatriCancer Therapies, Stem Cell Medicine, Murdoch Children's Research Institute, Parkville, VIC, Australia.ORCID http://orcid.org/0009-0004-3096-6022
Pamala A JacobsonDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-4145-7045
David MetzDepartment of Nephrology, Royal Children's Hospital, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0003-4478-5308
Daniel J CronaDivision of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, 120 Mason Farm Road, CB 7361, Genetic Medicine Building 2090, Chapel Hill, NC, 27599, USA. daniel.crona@unc.edu.ORCID http://orcid.org/0000-0003-3742-8863

Funding

PharmGKB: pharmacogenomics discovery and implementationU24HG010615 · NHGRI · STANFORD UNIVERSITY · PI TERI Ellen KLEIN, Michelle Whirl-Carrillo · 2020 to 2026
$9.5M
Clinical Implementation Resources for Pharmacogenomics (CIRP)U24HG013077 · NHGRI · STANFORD UNIVERSITY · PI CAUDLE, KELLY E., KLEIN, TERI ELLEN · 2023 to 2025
$4.4M
Enhancement Training for the Next Generation of Translational Ph.D. ScientistsT32GM122741 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WOLBERG, ALISA S., YEH, JEN JEN · 2018 to 2022
$898k
Medical Research Future Fund MRF/2024900NHGRI NIH HHS U24HG010615NHGRI NIH HHS U24HG013077NIGMS NIH HHS T32GM122741
6 · The paper itself

Abstract

Tacrolimus is a narrow therapeutic index drug with wide intrapatient and interpatient pharmacokinetic variability and cytochrome P450 3A5 (CYP3A5) genotype-guided dosing recommendations. This review aimed to evaluate population pharmacokinetic models and dosing algorithms across all treatment settings that analyzed the influence of CYP3A5 genotypic variation plus additional clinical covariates on tacrolimus pharmacokinetics. These effects were mathematically translated and summarized to provide a comparison between models. Changes in apparent clearance warranting tacrolimus dose adjustments were assessed and summarized by relative magnitude and direction. Sixty-eight tacrolimus population pharmacokinetic models were included in this review, including 55 developed for adults and 38 for kidney transplant recipients. The most frequently retained covariates on tacrolimus clearance were CYP3A5 genotype (88%), body size (29%), hematocrit (29%), and days since transplant (28%). The median fold increase in apparent clearance, across all treatments, was 1.64 for CYP3A5 normal and intermediate metabolizer patients compared to poor metabolizer patients. As days since transplant increased, median tacrolimus apparent clearance increased in liver (n = 6) and lung transplant (n = 2) models but decreased early post-transplant and then subsequently increased in kidney transplant models (n = 11). Concomitant administration of tacrolimus with -azole antifungals or Wuzhi capsules was associated with reduced tacrolimus apparent clearance (38% and 31%, respectively), while corticosteroids were associated with a 23% increase in apparent clearance. Based on our analysis, a substantial tacrolimus dose increase (≥ 75%) is required for CYP3A5 normal and intermediate metabolizer patients compared with poor metabolizer patients. Ultimately, these findings can be used to determine optimal personalized tacrolimus doses across a variety of disease states and treatment types.

Identifiers

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.