Binding of Drugs to Sera of Patients with Renal Disease and Liver Disease

Abstract

The drug binding characteristics of pooled sera from patients with acute or chronic hepatitis and with chronic renal failure were investigated by means of equilibrium dialysis and ultracentrifugation, and were compared with those of healthy adult serum and human serum albumin. The drugs used were diazepam, naproxen, warfarin, and phenylbutazone. Serum from patients with renal disease showed markedly impaired binding with diazepam and naproxen at the primary binding site. However, almost no decrease of the binding was observed with warfarin and phenylbutazone. The impaired bindings of diazepam and naproxen were restored after active-charcoal treatment of the serum. This result suggested that, in the serum from patients with renal disease, the apparent decrease of the binding is probably due to the presence of some substance (s) which inhibit the binding of these drugs to the primary sites. On the other hand, no abnormal binding behavior was recognized in the serum from patients with liver disease. Thus, care is necessary when drugs binding to the diazepam site (such as diazepam and naproxen) are administered to patients with renal diseases, because a marked elevation of unbound drug concentration in the serum may occur.