Investigation of distribution and elimination of terbutaline sulfate in the perfused rat liver preparation

Hepatic distribution and elimination of terbutaline sulfate (TBS) was investigated in the in situ isolated perfused rat liver preparation. Perfusion experiments were conducted using Krebs bicarbonate buffer delivered via the portal vein in a single-pass mode at a total flow rate of 15 mL min⁻¹. TBS was administered as a bolus (2 mg mL⁻¹) in the absence and presence of erythrocytes (50% hematocrit) or albumin (1%). Immediately after a bolus administration, the outflow perfusate was collected and then concentration of TBS was determined by a validated HPLC method. Regardless of the condition, the extraction of TBS (0.35–0.51) across the liver during single pass was intermediate. Although protein binding of TBS was very low (2.5%), it was taken up slowly and continuously by erythrocytes. A blood to plasma concentration ratio of 2.8 obtained at the end of incubation period clearly indicates that TBS has an affinity to erythrocytes. However, under the conditions used in this study, hepatic distribution and elimination of TBS were not influenced by the presence of erythrocytes or albumin.