S. Bianco

Time-dependent modifications of splanchnic circulation in female pigs submitted to end-to-side portacaval anastomosis.

Fractional systemic bioavailability of orally administered drugs was found to be unexpectedly low in liver cirrhosis, even after surgical portal–systemic shunting. Fecal loss or intestinal first-pass elimination were assumed to explain the finding. In this paper we evaluated alternative pathophysiological interpretations relating low bioavailability to adaptive circulatory modifications. d-Sorbitol was used because its hepatic extraction is very high and hepatic removal follows a flow-dependent clearance regimen. d-Sorbitol bioavailability was measured at steady state in pigs submitted to end-to-side portacaval anastomosis, immediately after surgery and four weeks later. Intestinal first-pass elimination dependent on fecal loss and intraluminal degradation was excluded by administering D-sorbitol into the superior mesenteric artery. Almost complete bioavailability was observed immediately after surgery (N = 6, 0.96 ± 0.08); four weeks later the bioavailability dropped (−36.8 ± 18.7%; P < 0.001) while hepatic clearance significantly increased (+83.6 ± 47.9%; P < 0.01). Experimental data support the hypothesis that adaptive circulatory changes spontaneously occur after some time, leading to a lower than expected portal bioavailability.