Assessment of hepatic blood flow using continuous infusion of high clearance drugs.
OBJECTIVE
To provide methods for the translation of the concentration-time profile of highly cleared marker compounds into the underlying clearance and hepatic blood flow profile.


METHODS
Continuous infusion of indocyanine green or sorbitol was used to assess the effect of the hepatic blood flow modifiers exercise, somatostatin and octreotide. Three distinct methods are described for the translation of concentration into flow: 1. assuming successive phases of constant clearance 2. point to point estimation of clearance using estimates of concentration change 3. using a parametric description of the flow profile in combination with the differential equations describing the change in marker concentrations.


RESULTS
The marker compound concentration profiles are adequately described using the different methods. Exercise results in a decrease in hepatic blood flow of about 80%. Somatostatin and octreotide elicit an indistinguishable hepatic blood flow decrease from 1.49 to 1.07 l min(-1). Return to baseline takes much longer for octreotide (half-life 126+/-104 min) than for somatostatin (half-life 4.29+/-3.55 min).


CONCLUSIONS
Translation of concentration profiles into clearance profiles is possible making continuous assessment of hepatic blood flow feasible.
Schoemaker
R C
RC
Centre for Human Drug Research, Leiden, The Netherlands.
Burggraaf
J
J
Cohen
A F
AF
D004396:Coloring Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D015444:Exercise / Q000502:physiology*; D006207:Half-Life; D006727:Hormone Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D006728:Hormones / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007208:Indocyanine Green / Q000008:administration & dosage / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D008102:Liver Circulation / Q000187:drug effects; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D015282:Octreotide / Q000493:pharmacokinetics / Q000494:pharmacology*; D013004:Somatostatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D013012:Sorbitol / Q000008:administration & dosage / Q000493:pharmacokinetics
D004396:Coloring Agents; D006727:Hormone Antagonists; D006728:Hormones; D007202:Indicators and Reagents; D013012:Sorbitol; D013004:Somatostatin; D007208:Indocyanine Green; D015282:Octreotide