Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018;40:526–48.

CAS  PubMed  Google Scholar 

Barre J, Didey F, Delion F, Tillement J-P. Problems in therapeutic drug monitoring: free drug level monitoring. Ther Drug Monit. 1988;10:133.

CAS  PubMed  Google Scholar 

Gugler R, Mueller G. Plasma protein binding of valproic acid in healthy subjects and in patients with renal disease. Br J Clin Pharmacol. 1978;5:441–6.

CAS  PubMed  PubMed Central  Google Scholar 

Brown CS, Liu J, Riker RR, Mara KC, Rabinstein AA, Fraser GL, et al. Evaluation of free valproate concentration in critically ill patients. Crit Care Explor. 2022;4:e0746.

PubMed  PubMed Central  Google Scholar 

Riker RR, Gagnon DJ, Hatton C, May T, Seder DB, Stokem K, et al. Valproate protein binding is highly variable in ICU patients and not predicted by total serum concentrations: a case series and literature review. Pharmacotherapy. 2017;37:500–8.

CAS  PubMed  Google Scholar 

Dasgupta A. Usefulness of monitoring free (unbound) concentrations of therapeutic drugs in patient management. Clin Chim Acta. 2007;377:1–13.

CAS  PubMed  Google Scholar 

Dautzenberg G, Nederlof M, Beekman A, Egberts T, Heerdink ER. Severe cognitive impairment associated with a high free but therapeutic total concentration of valproic acid due to hypoalbuminemia in an older patient with bipolar disorder. J Clin Psychopharmacol. 2018;38:265.

CAS  PubMed  Google Scholar 

Haroldson JA, Kramer LE, Wolff DL, Lake KD. Elevated free fractions of valproic acid in a heart transplant patient with hypoalbuminemia. Ann Pharmacother. 2000;34:183–7.

CAS  PubMed  Google Scholar 

Mayerhoff DI, Nurenberg J, Shah S, Schleifer SJ. Neurotoxicity associated with free valproic acid. Am J Psychiatry. 2005;162:810–810.

PubMed  Google Scholar 

de Maat MM, van Leeuwen HJ, Edelbroek PM. High unbound fraction of valproic acid in a hypoalbuminemic critically iii patient on renal replacement therapy. Ann Pharmacother. 2011;45:420–420.

Google Scholar 

Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.

CAS  PubMed  Google Scholar 

Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707–10.

CAS  PubMed  Google Scholar 

Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208.

PubMed  PubMed Central  Google Scholar 

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–81.

PubMed  Google Scholar 

Bates D, Mächler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Stat Soft. 2015;67:1–48.

Google Scholar 

Gibbs HG, Zimmerman DE, Shermock KM, Clarke W, Mirski MA, Lewin JJ III. Comparison of free fraction serum valproic acid concentrations between inpatients and outpatients. Am J Health-Syst Pharm. 2015;72:121–6.

CAS  PubMed  Google Scholar 

Fisch U, Baumann SM, Semmlack S, Marsch S, Rüegg S, Sutter R. Accuracy of calculated free valproate levels in adult patients with status epilepticus. Neurology. 2021;96:e102–10.

CAS  PubMed  Google Scholar 

Wallenburg E, Klok B, de Jong K, de Maat M, van Erp N, Stalpers-Konijnenburg S, et al. Monitoring protein-unbound valproic acid serum concentrations in clinical practice. Ther Drug Monit. 2017;39:269.

CAS  PubMed  Google Scholar 

Drisaldi A, Weeda E, Neyens R, Orvin N, Bonilha L, Campbell Z, et al. Accuracy of valproic acid concentration correction based on serum albumin. Neurocrit Care. 2019;30:301–6.

CAS  PubMed  Google Scholar 

Nasreddine W, Atweh SF, Beydoun AA, Dirani M, Nawfal O, Beydoun A. Predicting the occurrence of thrombocytopenia from free valproate levels: a prospective study. Seizure. 2022;94:33–8.

PubMed  Google Scholar 

Segura-Bruna N, Rodriguez-Campello A, Puente V, Roquer J. Valproate-induced hyperammonemic encephalopathy. Acta Neurol Scand. 2006;114:1–7.

CAS  PubMed  Google Scholar 

Vázquez M, Fagiolino P, Maldonado C, Olmos I, Ibarra M, Alvariza S, et al. Hyperammonemia associated with valproic acid concentrations. Biomed Res Int. 2014;2014:217269.

PubMed  PubMed Central  Google Scholar 

Baddour E, Tewksbury A, Stauner N. Valproic acid–induced hyperammonemia: incidence, clinical significance, and treatment management. Ment Health Clin. 2018;8:73–7.

PubMed  PubMed Central  Google Scholar 

Long MT, Coursin DB. Undifferentiated non-hepatic hyperammonemia in the ICU: diagnosis and management. J Crit Care. 2022;70:154042.

PubMed  Google Scholar 

Bowdle TA, Patel IH, Levy RH, Wilensky AJ. Valproic acid dosage and plasma protein binding and clearance. Clin Pharmacol Ther. 1980;28:486–92.

CAS  PubMed  Google Scholar 

Klotz U, Rapp T, Müller WA. Disposition of valproic acid in patients with liver disease. Eur J Clin Pharmacol. 1978;13:55–60.

CAS  PubMed  Google Scholar 

Devine E, Krieter DH, Rüth M, Jankovski J, Lemke H-D. Binding affinity and capacity for the uremic toxin indoxyl sulfate. Toxins. 2014;6:416–29.

PubMed  PubMed Central  Google Scholar 

Dasgupta A, Jacques M. Reduced in vitro displacement of valproic acid from protein binding by salicylate in uremic sera compared with normal sera. Role of uremic compounds. Am J Clin Pathol. 1994;101:349–53.

CAS  PubMed  Google Scholar 

Patel IH, Levy RH. Valproic acid binding to human serum albumin and determination of free fraction in the presence of anticonvulsants and free fatty acids. Epilepsia. 1979;20:85–90.

CAS  PubMed  Google Scholar 

Mike LA. Propofol-related infusion syndrome. Pract Gastroenterol. 2010;81:16–24.

Google Scholar 

Albani F, Riva R, Contin M, Baruzzi A, Altomare M, Merlini G, et al. Differential transplacental binding of valproic acid: influence of free fatty acids. Br J Clin Pharmacol. 1984;17:759–62.

CAS  PubMed  PubMed Central  Google Scholar 

de Leon J, Kiesel JL, Fleming MW, Strobl B. Valproic acid toxicity associated with low dose of aspirin and low total valproic acid levels: a case report. J Clin Psychopharmacol. 2009;29:509.

PubMed  Google Scholar 

Sandson NB, Marcucci C, Bourke DL, Smith-Lamacchia R. An interaction between aspirin and valproate: the relevance of plasma protein displacement drug-drug interactions. Am J Psychiatry. 2006;163:1891–6.

PubMed  Google Scholar 

Goulden KJ, Dooley JM, Camfield PR, Fraser AD. Clinical valproate toxicity induced by acetylsalicylic acid. Neurology. 1987;37:1392–1392.

CAS  PubMed  Google Scholar 

Fleitman JS, Bruni J, Perrin JH, Wilder BJ. Albumin-binding interactions of sodium valproate. J Clin Pharmacol. 1980;20:514–7.

CAS  PubMed  Google Scholar 

Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2009;48:143–57.

CAS  PubMed  PubMed Central  Google Scholar 

Loiseau P, Brachet A, Henry P. Concentration of dipropylacetate in plasma. Epilepsia. 1975;16:609–15.

CAS  PubMed  Google Scholar