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Diazepam and lidocaine plasma protein binding in renal disease
Author(s) -
Grossman Steven H,
Davis Dwight,
Kitchell Barbara B,
Shand David G,
Routledge Philip A
Publication year - 1982
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1982.45
Subject(s) - lidocaine , uremia , medicine , nephrotic syndrome , diazepam , endocrinology , albumin , orosomucoid , gastroenterology , chemistry , pharmacology , anesthesia , glycoprotein , biochemistry
The plasma protein binding of diazepam and lidocaine was measured in patients with renal disease (those with uremia, nephrotic syndrome, or who had received a transplant) and in age‐and sex‐matched control subjects. Percentage unbound diazepam in plasma was increased over control in all three groups of patients as follows: uremic patients 3.23%, control, 1.64% (P < 0.001), nephrotic patients, 3.55%, control, 1.63% (P < 0.001); and transplant recipients, 2.11%, control 1.50% (P < 0.001). The binding ratio (molar concentration of bound to unbound drug) in the patients was related to albumin concentration (r = 0.609, P < 0.001). Percentage of unbound lidocaine did not differ substantially from control in nephrotic patients (34.2%, control 30.8%), but was reduced in the uremic patients (20.8%, control 30.7%, P < 0.001) and transplant recipients (24.6%, control 33.7%, P < 0.005). These increases were associated with increases in α 1 ‐acid glycoprotein (AAG) concentration (uremic patients 134.9 mg/dl, control 66.3, P < 0.001; transplant recipients 106.5, control 65.6, P < 0.001). The binding ratio of lidocaine was closely related to the AAG concentration in patients (r = 0.933, P < 0.001) and controls (r = 0.719, P < 0.001). Thus, the binding of basic drugs may be increased or decreased in patients with renal disease, depending on the relative contribution of the individual plasma proteins to the total binding and the type of disease. Clinical Pharmacology and Therapeutics (1982) 31, 350–357; doi: 10.1038/clpt.1982.45