Diazepam and lidocaine plasma protein binding in renal disease

Abstract

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 3 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 .alpha.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). 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.