Evidence map›Paper›PMID 12190331›Full record

ReviewClinical pharmacokinetics2002

Mechanisms of clinically relevant drug interactions associated with tacrolimus.

Uwe Christians, Wolfgang Jacobsen, Leslie Z Benet, Alfonso Lampen

Abstract readReview
PubMed Publisher
In one paragraph

Review in Clinical pharmacokinetics, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 1 pooled it
9.1field-weighted citation impact, top 2% of its field
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

106 citing papers in PubMed, 1 synthesis or guideline pooled it, 313 citations in OpenAlex.

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  18. State of Art of Dose Individualization to Support tacrolimus drug monitoring: What's Next?Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  19. Effect ofCurrent drug metabolism · 2025
    Article
  20. Article

46 more citing papers are in PubMed but not listed here.

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

4 authors at 3 institutions in 2 countries.

Uwe ChristiansDepartment of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado, USA. uwe.christians@uchsc.edu
Wolfgang Jacobsen
Leslie Z Benet
Alfonso Lampen
University of Colorado Health · USMedizinische Hochschule Hannover · DEUniversity of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The clinical management of tacrolimus, a macrolide used as immunosuppressant after transplantation, is complicated by its narrow therapeutic index in combination with inter- and intraindividually variable pharmacokinetics. As a substrate of cytochrome P450 (CYP) 3A enzymes and P-glycoprotein, tacrolimus interacts with several other drugs used in transplantation medicine, which also are known CYP3A and/or P-glycoprotein inhibitors and/or inducers. In clinical studies, CYP3A/P-glycoprotein inhibitors and inducers primarily affect oral bioavailability of tacrolimus rather than its clearance, indicating a key role of intestinal P-glycoprotein and CYP3A. There is an almost complete overlap between the reported clinical drug interactions of tacrolimus and those of cyclosporin. However, in comparison with cyclosporin, only few controlled drug interaction studies have been carried out, but tacrolimus drug interactions have been extensively studied in vitro. These results are inconsistent and are of poor predictive value for clinical drug interactions because of false negative results. P-glycoprotein regulates distribution of tacrolimus through the blood-brain barrier into the brain as well as distribution into lymphocytes. Interaction of other drugs with P-glycoprotein may change tacrolimus tissue distribution and modify its toxicity and immunosuppressive activity. There is evidence that ethnic and gender differences exist for tacrolimus drug interactions. Therapeutic drug monitoring to guide dosage adjustments of tacrolimus is an efficient tool to manage drug interactions. In the near future, progress can be expected from studies evaluating potential pharmacokinetic interactions caused by herbal preparations and food components, the exact biochemical mechanism underlying tacrolimus toxicity, and the potential of inhibition of CYP3A and P-glycoprotein to improve oral bioavailability and to decrease intraindividual variability of tacrolimus pharmacokinetics.

Indexed as

Adrenal Cortex HormonesAdultAge FactorsBiological AvailabilityChildDrug InteractionsDrug Resistance, MultipleFemaleHIV Protease InhibitorsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsImmunosuppressive AgentsMalePlant PreparationsPsychotropic DrugsRacial GroupsAdrenal Cortex HormonesHIV Protease InhibitorsHydroxymethylglutaryl-CoA Reductase InhibitorsImmunosuppressive AgentsPlant PreparationsPsychotropic DrugsTacrolimus

Identifiers

PMID12190331
OpenAlexW2086575226

What Socratic holds

Textmetadata
Read underepoch 390

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.