ArticleTherapeutic drug monitoring2012
Pharmacokinetics of tacrolimus during pregnancy.
Article in Therapeutic drug monitoring, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07422012 (Optimization of Tacrolimus Management During Pregnancy), which is not on this map. Cited by 39 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Optimization of Tacrolimus Management During Pregnancy: Modeling of Unbound and Whole Blood Tacrolimus in Pregnant Uterus Transplant Recipients
Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 115 citations in OpenAlex.
- Adverse Pregnancy Outcomes in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis.JAMA network open · 2024Pooled it
- Toward a robust tool for pharmacokinetic-based personalization of treatment with tacrolimus in solid organ transplantation: A model-based meta-analysis approach.British journal of clinical pharmacology · 2019Pooled it
- Unbound Plasma, Total Plasma, and Whole-Blood Tacrolimus Pharmacokinetics Early After Thoracic Organ Transplantation.Clinical pharmacokinetics · 2020Trial
- Tacrolimus exposure during pregnancy in kidney and liver transplantation recipients: A comparison between whole blood and plasma concentration-to-dose ratios.British journal of clinical pharmacology · 2026Article
- Pregnancy in Patients With Renal Transplant.O&G open · 2026Review
- Machine Learning Models Reveal New Risk Factors for Sub-/Supra-Therapeutic Concentrations of Sirolimus in Children with Vascular Anomalies.Drug design, development and therapy · 2026Article
- Approach to the prevention of atypical hemolytic uremic syndrome recurrence using eculizumab in a pregnant kidney transplant recipient with complement factor H gene mutation: a case report and literature review.Journal of nephrology · 2025Review
- Myasthenia gravis complicated by pure red cell aplasia with clonal large granular lymphocytosis in the absence of thymoma: a rare case report and literature review.Frontiers in immunology · 2025Review
- An Immune-Independent Mode of Action of Tacrolimus in Promoting Human Extravillous Trophoblast Migration Involves Intracellular Calcium Release and F-Actin Cytoskeletal Reorganization.International journal of molecular sciences · 2024Article
- Steroid-tacrolimus drug-drug interaction and the effect of CYP3A genotypes.British journal of clinical pharmacology · 2024Article
- Article
- Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort.Transplantation direct · 2023Article
- Design Considerations for Pharmacokinetic Studies During Pregnancy.Journal of clinical pharmacology · 2023Article
- Fetal endothelial colony-forming cell impairment after maternal kidney transplantation.Pediatric research · 2023Article
- Article
- Impact of Pregnancy on GFR Decline and Kidney Histology in Kidney Transplant Recipients.Kidney international reports · 2022Article
- Pharmacokinetic data in pregnancy: A review of available literature data and important considerations in collecting clinical data.Frontiers in medicine · 2022Review
- Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients.Frontiers in immunology · 2021Article
- Sources of Interindividual Variability.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Case Report: Low Hematocrit Leading to Tacrolimus Toxicity.Frontiers in pharmacology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundInformation on the pharmacokinetics of tacrolimus during pregnancy is limited to case reports despite the increasing number of pregnant women being prescribed tacrolimus for immunosuppression.
methodsBlood, plasma, and urine samples were collected over 1 steady-state dosing interval from women treated with oral tacrolimus during early to late pregnancy (n = 10) and postpartum (n = 5). Total and unbound tacrolimus as well as metabolite concentrations in blood and plasma were assayed by a validated liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) method. A mixed-effect linear model was used for comparison across gestational age and using postpartum as the reference group.
resultsThe mean oral clearance (CL/F) based on whole-blood tacrolimus concentration was 39% higher during mid-pregnancy and late pregnancy compared with postpartum (47.4 ± 12.6 vs. 34.2 ± 14.8 L/h, P < 0.03). Tacrolimus-free fraction increased by 91% in plasma (f(P)) and by 100% in blood (f(B)) during pregnancy (P = 0.0007 and 0.002, respectively). Increased fP was inversely associated with serum albumin concentration (r = -0.7, P = 0.003), which decreased by 27% during pregnancy. Pregnancy-related changes in f(P) and f(B) contributed significantly to the observed gestational increase in tacrolimus whole-blood CL/F (r² = 0.36 and 0.47, respectively, P < 0.01). In addition, tacrolimus whole-blood CL/F was inversely correlated with both hematocrit and red blood cell counts, suggesting that binding of tacrolimus to erythrocytes restricts its availability for metabolism. Treating physicians increased tacrolimus dosages in study participants during pregnancy by an average of 45% to maintain tacrolimus whole-blood trough concentrations in the therapeutic range. This led to striking increases in unbound tacrolimus trough concentrations and unbound area under the concentration-time curve, by 112% and 173%, respectively, during pregnancy (P = 0.02 and 0.03, respectively).
conclusionsTacrolimus pharmacokinetics are altered during pregnancy. Dose adjustment to maintain whole-blood tacrolimus concentration in the usual therapeutic range during pregnancy increases circulating free drug concentrations, which may impact clinical outcomes.
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Registered trials
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 OpenQuestion graph.