Sorbitol as a marker for drug-induced decreases of variable duration in liver blood flow in healthy volunteers

Objective: Sorbitol has been suggested as a suitable marker to assess liver blood flow (LBF), after it was shown to adequately reflect prolonged chang es in LBF but changes of a shorter duration have not been investigated. We therefore used sorbitol to evaluate drug-induced decreases in LBF of variab le duration with i.v. infusions of somatostatin and its synthetic analogue octreotide. Methods: In a double-blind, placebo controlled, randomised stud y, six healthy males received sorbitol for 170 min. At sorbitol steady stat e, which was at 45 min after the start of the infusion (t = 0), somatostati n or octreotide was infused for 30 min. Sampling for sorbitol assay and ech o-Doppler hepatic portal vein flow measurements were done regularly and tre atments were compared using ANOVA. Results: The sorbitol AUC over the 30-mi n intervention period was 15% (95% C.I.: +4, +22%) and 13% (+5, +24%) highe r compared to placebo after somatostatin and octreotide respectively. The d ecline of sorbitol levels after termination of the intervention was faster for somatostatin compared to octreotide, demonstrated by the difference in the AUC (0-2 h) with placebo which was 8% (-3, +19%) lower after somatostat in, and 15% (+5, +26%) after octreotide. Portal venous blood flow decreased during the 30-min interventions; after somatostatin 27% (-14, -40%) and af ter octreotide 29% (-17, -42%). Portal flow was lower than placebo during t he entire experiment after octreotide 30% (-10, -50%), but not after somato statin 13% (-33, +7%). Changes in sorbitol levels and portal venous blood f low occurred simultaneously and were well correlated for each individual, m aking it likely that the interventions did not interfere with metabolism. C onclusion: Sorbitol can be used to adequately assess decreases in LBF of va riable duration in healthy volunteers. (C) 2000 Elsevier Science B.V. All r ights reserved.