Sorbitol as a marker for drug-induced decreases of variable duration in liver blood flow in healthy volunteers
Burggraaf, J.; Schoemaker, R.C.; Lentjes, E.G.; Cohen, A.F.
European Journal of Pharmaceutical Sciences Official Journal of the European Federation for Pharmaceutical Sciences 12(2): 133-139
Objective: Sorbitol has been suggested as a suitable marker to assess liver blood flow (LBF), after it was shown to adequately reflect prolonged changes in LBF but changes of a shorter duration have been investigated. We therefore used sorbitol to evaluate drug-induced decreases in LBF of variable duration with i.v. infusions of somatostatin and its synthetic analogue octreotide. Methods: In a double-blind, placebo controlled, randomised study, six healthy males received sorbitol for 170 min. At sorbitol steady state, which was at 45 min after the start of the infusion (t=0), somatostatin or octreotide was infused for 30 min. Sampling for sorbitol assay and echo-Doppler hepatic portal vein flow measurements were done regularly and treatments were compared using ANOVA. Results: The sorbitol AUC over the 30-min intervention period was 15% (95% C.I.: +4, +22%) and 13% (+5, +24%) higher compared to placebo after somatostatin and octreotide respectively. The decline 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 somatostatin, and 15% (+5, +26%) after octreotide. Portal venous blood flow decreased during the 30-min interventions; after somatostatin 27% (-14, -40%) and after octreotide 29% (-17, -42%). Portal flow was lower than placebo during the entire experiment after octreotide 30% (-10, -50%), but not after somatostatin 13% (-33, +7%). Changes in sorbitol levels and portal venous blood flow occurred simultaneously and were well correlated for each individual, making it likely that the interventions did not interfere with metabolism. Conclusion: Sorbitol can be used to adequately assess decreases in LBF of variable duration in healthy volunteers.