title: Comparison of free fraction serum valproic acid concentrations between inpatients and outpatients.
abstract: OBJECTIVE
  The differences in free fraction serum valproic acid concentrations between inpatients and outpatients were compared, and factors associated with therapeutic discordance were evaluated.
  
  
  METHODS
  This retrospective, single-center, cross-sectional study included patients with both a free and a total valproic acid concentration drawn within 30 minutes of each other between January 7, 2003, and June 1, 2011. Serum valproic acid concentrations were stratified by admission status (inpatient versus outpatient). In the primary analysis, for patients who had multiple paired concentrations drawn, one free valproic acid level and one total valproic acid level (i.e., one pair) were chosen at random for each inpatient. Information regarding patient demographics, laboratory data, and concomitant medication therapy was collected. Single and multivariable logistic regressions were performed to determine the odds of therapeutic discordance.
  
  
  RESULTS
  During the study period, inpatient concentrations were measured in 220 patients, and outpatient concentrations were measured in 41 patients. The median total valproic acid concentration in the inpatient group was significantly lower than that in the outpatient group (54 μg/mL versus 83 μg/mL, p < 0.001). The median free fraction of inpatient levels was nearly twice as high as that of outpatient levels (28.8% versus 15.5%, p < 0.001). Levels drawn in inpatients were therapeutically discordant 63% of the time compared to only 19% in outpatients (p < 0.001). Multivariable logistic regression identified low albumin as an independent risk factor for therapeutic discordance.
  
  
  CONCLUSIONS
  The median free fraction of valproic acid was significantly higher in inpatients than in outpatients. Low albumin concentration was a predictor of discordance between free and total valproic acid concentrations.
authors.affiliation: Haley G. Gibbs, Pharm. D., is Clinical Pharmacy Specialist, Department of Pharmacy, Johns Hopkins Hospital (JHH), Baltimore, MD. David E. Zimmerman, Pharm.D., is Assistant Professor of Pharmacy, Department of Clinical, Social, and Administrative Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA. Kenneth M. Shermock, Pharm.D., Ph. D., is Director of the Center for Medication Quality and Outcomes, Department of Pharmacy; William Clarke, Ph.D., is Associate Professor, Director of Clinical Toxicology, Department of Clinical Toxicology; Marek A. Mirski, M.D., Ph.D., is Vice-Chair and Director, Neuroscience Critical Care Unit, Department of Anesthesiology and Critical Care Medicine; and John J. Lewin III, Pharm.D., M.B.A., is Division Director, Critical Care and Surgery Pharmacy, Department of Pharmacy, and Adjunct Assistant Professor, Department of Anesthesiology and Critical Care Medicine, JHH. hgoodwi3@jhmi.edu.
authors.forename: Haley G
authors.initials: HG
authors.lastname: Gibbs
authors.affiliation: Haley G. Gibbs, Pharm. D., is Clinical Pharmacy Specialist, Department of Pharmacy, Johns Hopkins Hospital (JHH), Baltimore, MD. David E. Zimmerman, Pharm.D., is Assistant Professor of Pharmacy, Department of Clinical, Social, and Administrative Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA. Kenneth M. Shermock, Pharm.D., Ph. D., is Director of the Center for Medication Quality and Outcomes, Department of Pharmacy; William Clarke, Ph.D., is Associate Professor, Director of Clinical Toxicology, Department of Clinical Toxicology; Marek A. Mirski, M.D., Ph.D., is Vice-Chair and Director, Neuroscience Critical Care Unit, Department of Anesthesiology and Critical Care Medicine; and John J. Lewin III, Pharm.D., M.B.A., is Division Director, Critical Care and Surgery Pharmacy, Department of Pharmacy, and Adjunct Assistant Professor, Department of Anesthesiology and Critical Care Medicine, JHH.
authors.forename: David E
authors.initials: DE
authors.lastname: Zimmerman
authors.affiliation: Haley G. Gibbs, Pharm. D., is Clinical Pharmacy Specialist, Department of Pharmacy, Johns Hopkins Hospital (JHH), Baltimore, MD. David E. Zimmerman, Pharm.D., is Assistant Professor of Pharmacy, Department of Clinical, Social, and Administrative Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA. Kenneth M. Shermock, Pharm.D., Ph. D., is Director of the Center for Medication Quality and Outcomes, Department of Pharmacy; William Clarke, Ph.D., is Associate Professor, Director of Clinical Toxicology, Department of Clinical Toxicology; Marek A. Mirski, M.D., Ph.D., is Vice-Chair and Director, Neuroscience Critical Care Unit, Department of Anesthesiology and Critical Care Medicine; and John J. Lewin III, Pharm.D., M.B.A., is Division Director, Critical Care and Surgery Pharmacy, Department of Pharmacy, and Adjunct Assistant Professor, Department of Anesthesiology and Critical Care Medicine, JHH.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Shermock
authors.affiliation: Haley G. Gibbs, Pharm. D., is Clinical Pharmacy Specialist, Department of Pharmacy, Johns Hopkins Hospital (JHH), Baltimore, MD. David E. Zimmerman, Pharm.D., is Assistant Professor of Pharmacy, Department of Clinical, Social, and Administrative Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA. Kenneth M. Shermock, Pharm.D., Ph. D., is Director of the Center for Medication Quality and Outcomes, Department of Pharmacy; William Clarke, Ph.D., is Associate Professor, Director of Clinical Toxicology, Department of Clinical Toxicology; Marek A. Mirski, M.D., Ph.D., is Vice-Chair and Director, Neuroscience Critical Care Unit, Department of Anesthesiology and Critical Care Medicine; and John J. Lewin III, Pharm.D., M.B.A., is Division Director, Critical Care and Surgery Pharmacy, Department of Pharmacy, and Adjunct Assistant Professor, Department of Anesthesiology and Critical Care Medicine, JHH.
authors.forename: William
authors.initials: W
authors.lastname: Clarke
authors.affiliation: Haley G. Gibbs, Pharm. D., is Clinical Pharmacy Specialist, Department of Pharmacy, Johns Hopkins Hospital (JHH), Baltimore, MD. David E. Zimmerman, Pharm.D., is Assistant Professor of Pharmacy, Department of Clinical, Social, and Administrative Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA. Kenneth M. Shermock, Pharm.D., Ph. D., is Director of the Center for Medication Quality and Outcomes, Department of Pharmacy; William Clarke, Ph.D., is Associate Professor, Director of Clinical Toxicology, Department of Clinical Toxicology; Marek A. Mirski, M.D., Ph.D., is Vice-Chair and Director, Neuroscience Critical Care Unit, Department of Anesthesiology and Critical Care Medicine; and John J. Lewin III, Pharm.D., M.B.A., is Division Director, Critical Care and Surgery Pharmacy, Department of Pharmacy, and Adjunct Assistant Professor, Department of Anesthesiology and Critical Care Medicine, JHH.
authors.forename: Marek A
authors.initials: MA
authors.lastname: Mirski
authors.affiliation: Haley G. Gibbs, Pharm. D., is Clinical Pharmacy Specialist, Department of Pharmacy, Johns Hopkins Hospital (JHH), Baltimore, MD. David E. Zimmerman, Pharm.D., is Assistant Professor of Pharmacy, Department of Clinical, Social, and Administrative Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA. Kenneth M. Shermock, Pharm.D., Ph. D., is Director of the Center for Medication Quality and Outcomes, Department of Pharmacy; William Clarke, Ph.D., is Associate Professor, Director of Clinical Toxicology, Department of Clinical Toxicology; Marek A. Mirski, M.D., Ph.D., is Vice-Chair and Director, Neuroscience Critical Care Unit, Department of Anesthesiology and Critical Care Medicine; and John J. Lewin III, Pharm.D., M.B.A., is Division Director, Critical Care and Surgery Pharmacy, Department of Pharmacy, and Adjunct Assistant Professor, Department of Anesthesiology and Critical Care Medicine, JHH.
authors.forename: John J
authors.initials: JJ
authors.lastname: Lewin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D012189:Retrospective Studies; D014635:Valproic Acid / Q000097:blood*; D055815:Young Adult
chemical_list: D014635:Valproic Acid