Influence of erythrocytes on the hepatic distribution kinetics of urea and thiourea

Sahin S., Rowland M.

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol.31, pp.180-189, 2007 (SCI-Expanded) identifier identifier identifier


The role of erythrocyte on the hepatic distribution kinetics of urea and thiourea was investigated in the in situ isolated perfused rat liver. 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. With urea, superimposable unimodal effluent curves were obtained in the presence and absence of erythrocytes, indicating that its distribution kinetics is not affected by erythrocytes. With thiourea, effluent curves were unimodal in the absence of erythrocytes but bimodal in the presence of erythrocytes. The maximum frequency output at the first peak increased from 0.017 +/- 0.002 to 0.042 +/- 0.006 s(-1) with an increase in the bolus hematocrit from 0.40 to 0.75, indicating that some thiourea fraction is retained by the erythrocytes on transit through the liver. Although the fractional output associated with the first peak was very similar (11.9% versus 11.5%), whether the perfusate contained unlabelled thiourea or not, this fraction was reduced from 17 to 5% with a decrease in the incubation time before injection from 30 min to 40 s. However, there was no evidence for a capacity limitation; a 30-min period of pre-incubation of either radiolabelled thiourea alone or combined with a high concentration of unlabelled thiourea had minimal effect on effluent profiles. (c) 2007 Elsevier B.V. All rights reserved.