期刊
THERAPEUTIC DRUG MONITORING
卷 26, 期 1, 页码 40-43出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00007691-200402000-00009
关键词
albumin; alpha-1; acid glycoprotein; binding; drugs; equilibrium dialysis
The binding of acetaminophen, lidocaine, phenobarbital, phenytoin, theophylline, and valproic acid to human serum alpha-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 alpha-1 acid glycoprotein. However, lidocaine and phenytoin demonstrated binding to this protein, and increases in the alpha-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.
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