ArticleClinical pharmacology and therapeutics2011
In vivo CYP3A activity is significantly lower in cyclosporine-treated as compared with tacrolimus-treated renal allograft recipients.
Article in Clinical pharmacology and therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04608474 (Lipid Management in Renal Transplant Recipients), which is not on this map. Cited by 16 papers.
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.
Lipid Management in Renal Transplant Recipients: a Pilot Study Evaluating the Use of a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK-9) Inhibitor Evolocumab.
Who cites it
16 citing papers in PubMed, 41 citations in OpenAlex.
- P-Glycoprotein and Breast Cancer Resistance Protein Transporter Inhibition by Cyclosporine and Quinidine on the Pharmacokinetics of Oral Rimegepant in Healthy Subjects.Clinical pharmacology in drug development · 2022Trial
- Perpetrator effects of ciclosporin (P-glycoprotein inhibitor) and its combination with fluconazole (CYP3A inhibitor) on the pharmacokinetics of rivaroxaban in healthy volunteers.British journal of clinical pharmacology · 2019Trial
- Trial
- Unveiling hepatic Krüppel-like factor 15 as the key regulator of cyclosporine A metabolism and adverse effects.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Impact of P-gp inhibition on systemic exposure of pralsetinib and dosing considerations.Clinical and translational science · 2024Article
- Single Nucleotide Polymorphisms of CYP3A4 and CYP3A5 in Romanian Kidney Transplant Recipients: Effect on Tacrolimus Pharmacokinetics in a Single-Center Experience.Journal of clinical medicine · 2024Article
- Tacrolimus induces a pro-fibrotic response in donor-derived human proximal tubule cells dependent on common variants of the CYP3A5 and ABCB1 genes.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit.British journal of clinical pharmacology · 2015Article
- The CYP3A4*22 C>T single nucleotide polymorphism is associated with reduced midazolam and tacrolimus clearance in stable renal allograft recipients.The pharmacogenomics journal · 2015Article
- The investigation of correlation between Iminoral concentration and neurotoxic levels after kidney transplantation.Advanced biomedical research · 2015Article
- Cyclosporine-inhibitable cerebral drug transport does not influence clinical methadone pharmacodynamics.Anesthesiology · 2014Article
- Calcineurin inhibitor sparing strategies in renal transplantation, part one: Late sparing strategies.World journal of transplantation · 2014Review
- Comparison of the influence of cyclosporine and tacrolimus on the pharmacokinetics of prednisolone in adult male kidney transplant recipients.Clinical drug investigation · 2014Observational
- Cyclosporine-inhibitable blood-brain barrier drug transport influences clinical morphine pharmacodynamics.Anesthesiology · 2013Article
- Cyclosporine inhibition of hepatic and intestinal CYP3A4, uptake and efflux transporters: application of PBPK modeling in the assessment of drug-drug interaction potential.Pharmaceutical research · 2013Article
- Importance of multi-p450 inhibition in drug-drug interactions: evaluation of incidence, inhibition magnitude, and prediction from in vitro data.Chemical research in toxicology · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vitro studies have identified cyclosporine and tacrolimus as CYP3A inhibitors. In the current study in renal allograft recipients, we used intravenously and orally administered midazolam as a drug probe to assess whether the study drugs at doses that are generally used in clinical practice have differential effects on in vivo hepatic and first-pass CYP3A activities. Systemic and apparent oral midazolam clearance were 24% (269 ± 73 vs. 354 ± 102 ml/min, P = 0.022) and 31% (479 ± 190 vs. 688 ± 265 ml/min, P = 0.013), respectively, lower in cyclosporine-treated patients (n = 20) than in matched tacrolimus-treated patients (n = 20). The latter displayed midazolam clearances similar to those in two larger cohorts of nonmatched tacrolimus-treated patients (n = 58 and n = 80) and to those receiving a calcineurin inhibitor-free regimen (n = 6). This implies that in vivo hepatic and first-pass CYP3A activities are significantly lower in patients receiving cyclosporine than in those receiving tacrolimus, indicating that, at the doses generally used in clinical practice, cyclosporine is the stronger of the two with respect to CYP3A inhibition. This observation has important implications in the context of drug-drug interactions in transplant recipients.
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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 Socratic graph.