Influence of Serum Protein Binding on the Pharmacokinetics of Quinidine in Normal and Anuric Rats

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Abstract
The pharmacokinetics of quinidine were investigated in normal and anuric rats after intravenous injection (25 mg per kg b. wt.). In normal rats only 2.6 percent of the injected dose was excreted as unchanged quinidine in the urine. Quinidine concentrations were determined in the blood and in different tissues after injection, and the serum protein binding was measured. Results were applied to a one compartment model. In normal rats a total body clearance of 18.5 ml/min. and a renal clearance of 0.5 ml/min. was found. The residual non‐renal clearance (18.0 ml/min.), presumably taking place in the liver, exceeds the estimated liver blood flow (16.8 ml/min.), indicating efficient extraction of quinidine from plasma and blood cells (non‐restrictive elimination). The apparent volume of distribution was greatly reduced, biological half‐life slightly longer and the body clearance greatly reduced in anuric as compared to normal rats. The fraction of unbound quinidine in serum was 30.6 ± 0.6 (n=23) and 16.7 ± 0.5) (n=23) percent in normal and anuric rats. The reduction in the apparent volume of distribution is mainly explained by increased serum binding. The decline of body clearance of quinidine is most likely caused by a decreased liver blood flow in this complex state of renal insufficiency.