| Hypoalbuminemia is a common complication among hospitalized patients. Albumin is characterized by its non-specific binding to drugs, which makes hypoalbuminemia of concern among clinicians. Significant care should be applied to drugs of high protein binding capacity where hypoalbuminemia tends to cause pharmacokinetic changes and, consequently, pharmacodynamic alterations. These changes require drug dose adjustments based on albumin level and kidney function as well. This case report highlights an explanation of events most likely occurring when acute hypoalbuminemia is recorded among critically ill patients. Ivabradine was a drug of choice to control inappropriate sinus tachycardia in a critically ill cancer patient where acute hypoalbuminemia was detected while kidneys were functioning properly (determined by eGFR) and liver enzymes, including SGOT and SGPT showed normal values. The effect of ivabradine was easily detected by monitoring the heart rate in the intensive care unit. Pharmacokinetic changes associated with acute hypoalbuminemia observed in the case were associated with a decrease in heart rate, which might be due to an increase in tissue concentration of ivabradine as a highly protein-bound drug, which led to an increase in volume of distribution and hence increased activity of the drug as long as liver and kidney functions remained intact. The rapid increment in fraction unbound drug was followed by an escalation of drug elimination where heart rate increased, then returned to normal values. This is how our body maintains homeostasis. Integrating different pharmacokinetic parameters represents an essential step in decision-making about dose adjustment in hypoalbuminemia. |
- Moramarco S, Morciano L, Morucci L, et al. Epidemiology of Hypoalbuminemia in Hospitalized Patients: A Clinical Matter or an Emerging Public Health Problem? Nutrients. 2020 Nov 27;12(12):3656. doi: 3390/nu12123656.
- Ulldemolins M, Roberts JA, Rello J, Paterson DL, Lipman J. The effects of hypoalbuminaemia on optimizing antibacterial dosing in critically ill Clin Pharmacokinet. 2011 Feb;50(2):99-110. doi: 10.2165/11539220-000000000-00000.
- Borer JS, Böhm M, Ford I, et al. Effect of ivabradine on recurrent hospitalization for worsening heart failure in patients with chronic systolic heart failure: the SHIFT Eur Heart J. 2012;33(22):2813-2820.
- Nazer LH, AbuSara AK, Kamal Y. Augmented renal clearance in critically ill patients with Cancer (ARCCAN Study): A prospective observational study evaluating prevalence and risk factors. Pharmacol Res Perspect. 2021 Apr;9(2):e00747. doi: 10.1002/prp2.747.
- Owusu Obeng A, Egelund EF, Alsultan A, Peloquin CA, Johnson JA. CYP2C19 polymorphisms and therapeutic drug monitoring of voriconazole: are we ready for clinical implementation of pharmacogenomics? Pharmacotherapy. 2014 Jul;34(7):703-18. doi: 10.1002/phar.1400.
- Agarwal MA, Sridharan A, Pimentel RC, et al. Ventricular Arrhythmia in Cancer Patients: Mechanisms, Treatment Strategies and Future Avenues. Arrhythm Electrophysiol 2023 May 29;12:e16. doi: 10.15420/aer.2023.04.
- Arensman Hannan K, Draper E, Cole KC, Mc Hugh J, Rivera CG, Abu Saleh O. Impact of hypoalbuminemia on clinical outcomes among patients with obesity treated with ceftriaxone. Antimicrob Agents Chemother. 2024 Apr 3;68(4):e0166323. doi: 10.1128/aac.01663-23.
- Fan SL, Miller NS, Lee J, Remick DG. Diagnosing sepsis - The role of laboratory medicine. Clin Chim Acta. 2016 Sep 1;460:203-10. doi: 10.1016/j.cca.2016.07.002.
- Choi HY, Noh YH, Cho SH, et al. Evaluation of pharmacokinetic and pharmacodynamic profiles and tolerability after single (2.5, 5, or 10 mg) and repeated (2.5, 5, or 10 mg bid for 4.5 days) oral administration of ivabradine in healthy male Korean volunteers. Clinical therapeutics. 2013 Jun 1;35(6):819-35.
- Gandia P, Decheiver S, Picard M, Guilhaumou R, Baklouti S, Concordet D. Hypoalbuminemia and pharmacokinetics: when the misunderstanding of a fundamental concept leads to repeated errors over decades. Antibiotics. 2023 Mar 4;12(3):515.
- Roberts JA, Pea F, Lipman J. The clinical relevance of plasma protein binding changes. Clinical pharmacokinetics. 2013 Jan;52:1-8.
- Celestin MN, Musteata FM. Impact of changes in free concentrations and drug-protein binding on drug dosing regimens in special populations and disease states. Journal of pharmaceutical sciences. 2021 Oct 1;110(10):3331-44.
- Patel M, Taskar KS, Zamek-Gliszczynski MJ. Importance of Hepatic Transporters in Clinical Disposition of Drugs and Their Metabolites. J Clin Pharmacol. 2016 Jul;56 Suppl 7:S23-39. doi: 10.1002/jcph.671.
- Ivanyuk A, Livio F, Biollaz J, Buclin T. Renal Drug Transporters and Drug Interactions. Clin Pharmacokinet. 2017 Aug; 56(8):825-892. doi: 1007/s40262-017-0506-8.
- Wiedermann CJ. Hypoalbuminemia as Surrogate and Culprit of Infections. Int J Mol Sci. 2021 Apr 26;22(9):4496. doi: 10.3390/ijms22094496.
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