Original ArticleThe Binding of Selected Therapeutic Drugs to Human Serum α-1 Acid Glycoprotein and to Human Serum Albumin In VitroBailey, David N. MD; Briggs, John R. BSAuthor Information From the Division of Laboratory Medicine, Department of Pathology, University of California, San Diego, California. Received for publication September 2, 2003; accepted October 27, 2003. Reprints: David N. Bailey, MD, Division of Laboratory Medicine, Department of Pathology, UCSD Medical Center, 200 West Arbor Drive, San Diego, California 92103-8320 (e-mail: [email protected]). Therapeutic Drug Monitoring: February 2004 - Volume 26 - Issue 1 - p 40-43 Buy Abstract The binding of acetaminophen, lidocaine, phenobarbital, phenytoin, theophylline, and valproic acid to human serum α-1 acid glycoprotein (orosomucoid) and to human serum albumin separately in vitro was investigated using equilibrium dialysis of the unlabeled drugs. Each drug was studied at a therapeutic concentration. Alpha-1 acid glycoprotein was studied at one elevated and two physiological concentrations, whereas albumin was studied at one physiological and two low concentrations. The nonphysiological concentrations were consistent with those that might be seen in a variety of clinical conditions. Acetaminophen, phenobarbital, theophylline, and valproic acid showed negligible binding to α-1 acid glycoprotein. However, lidocaine and phenytoin demonstrated binding to this protein, and increases in the α-1 acid glycoprotein concentration produced decreases in the unbound (free) or “active” concentration of these two drugs. All drugs but acetaminophen bound to albumin, and decreases in the albumin concentration yielded increases in the unbound (free) or “active” concentration of the remaining 5 drugs. These findings are significant when lidocaine, phenytoin, phenobarbital, theophylline, or valproic acid are used in patients with clinical conditions that may affect the concentration of these two binding proteins. © 2004 Lippincott Williams & Wilkins, Inc.