ArticleIntensive care medicine2012
Acute kidney injury reduces the hepatic metabolism of midazolam in critically ill patients.
Article in Intensive care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 60 citations in OpenAlex.
- Association of Acute Kidney Injury and Chronic Kidney Disease With Concentration-To-Dose Ratios of Midazolam and Its Main Metabolites in Critically Ill Adults.Fundamental & clinical pharmacology · 2026Observational
- Analgesic and sedative drug dosing in critically ill patients with Acute Kidney Injury undergoing different modalities of Kidney Replacement Therapy.Journal of anesthesia, analgesia and critical care · 2025Review
- Review on Kidney-Liver Crosstalk: Pathophysiology of Their Disorders.Cell journal · 2024Article
- Assessing Kidney Injury Induced by Mercuric Chloride in Guinea Pigs with In Vivo and In Vitro Experiments.International journal of molecular sciences · 2023Article
- Association of CYP3A5 polymorphisms and parathyroid hormone with blood level of tacrolimus in patients with end-stage renal disease.Clinical and translational science · 2021Article
- Differences in efficacy and safety of midazolam vs. dexmedetomidine in critically ill patients: A meta-analysis of randomized controlled trial.Experimental and therapeutic medicine · 2021Article
- VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia-reperfusion injury in rats.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018Article
- Characterization of Intestinal and Hepatic CYP3A-Mediated Metabolism of Midazolam in Children Using a Physiological Population Pharmacokinetic Modelling Approach.Pharmaceutical research · 2018Article
- Activation of Constitutive Androstane Receptor Ameliorates Renal Ischemia-Reperfusion-Induced Kidney and Liver Injury.Molecular pharmacology · 2018Article
- Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure.British journal of clinical pharmacology · 2018Article
- Proton pump inhibitor-induced exfoliative dermatitis: A case report.Experimental and therapeutic medicine · 2016Article
- Using tramadol to measure CYP2D6 metabolism in critically ill adults.Intensive care medicine · 2014Article
- Consequences of renal failure on non-renal clearance of drugs.Clinical pharmacokinetics · 2014Review
- [Methohexital for analgosedation of ventilated intensive care patients : prospective nonrandomized single center observational study on incidence of delirium].Der Anaesthesist · 2014Observational
- Xenobiotic metabolism: the effect of acute kidney injury on non-renal drug clearance and hepatic drug metabolism.International journal of molecular sciences · 2014Review
- Significant increase in plasma 4β-hydroxycholesterol concentration in patients after kidney transplantation.Journal of lipid research · 2013Article
- Year in review in Intensive Care Medicine 2012: I. Neurology and neurointensive care, epidemiology and nephrology, biomarkers and inflammation, nutrition, experimentals.Intensive care medicine · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAcute kidney injury (AKI) is a common and serious complication increasing morbidity and mortality from all causes of hospital admission. We have previously shown that AKI decreases midazolam metabolism, a substrate of the cytochrome P450 3A (CYP3A) enzymes and our primary aim was to determine if this effect is dependent on the severity of AKI. We also present preliminary data on the functional impact of different genotypes of CYP3A.
methodsCritically ill patients at risk of AKI and admitted to a general intensive care unit were categorised after initial resuscitation according to the RIFLE criteria for AKI. Midazolam (1mg) was administered and the serum concentration of midazolam measured at 4 h. Samples were taken for CYP3A genotyping.
resultsSeventy-three patients were assigned to categories R, I and F of the RIFLE criteria or C (controls). Midazolam concentrations (ng mL(-1)) increased significantly (p = 0.002) as the severity of AKI worsened [control 3.1 (1.4-5.9), risk 4.7 (1.3-10.3), injury 3.9 (2.0-11.1) and failure 6.8 (2.2-113.6)] and were predicted by the duration of AKI (p = 0.000) and γ-glutamyl transferase (p = 0.005) concentrations. Increasing BMI negatively predicted the midazolam concentration (p = 0.001). Preliminary data suggest this effect is diminished if the patient expresses functional CYP3A5.
conclusionIncreasing severity and duration of AKI are associated with decreased midazolam elimination. We propose that this is caused by impaired CYP3A activity secondary to AKI. The exact mechanism remains to be elucidated. This may have important implications for our drug treatment of critically ill patients.
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