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Comparative Study
. 1998 May;45(5):463-9.
doi: 10.1046/j.1365-2125.1998.00711.x.

Assessment of hepatic blood flow using continuous infusion of high clearance drugs

R C Schoemaker  1 , J Burggraaf, A F Cohen
Affiliations
Comparative Study

Assessment of hepatic blood flow using continuous infusion of high clearance drugs

R C Schoemaker et al. Br J Clin Pharmacol. 1998 May.

Abstract

Aims: 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.

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Figures

Figure 1
Figure 1
Theoretical relationship between total hepatic blood flow and plasma clearance for ICG (•/○) and sorbitol (▪/□); filled markers: well-stirred model; open markers: parallel tube model
Figure 2
Figure 2
Observed (mean±s.d.) plasma ICG profile (–•–•–) and predicted (mean) plasma ICG profile assuming constant clearance for the three phases (——)
Figure 3
Figure 3
Calculated ICG plasma clearance. Predictions (mean) assuming constant clearance for the three phases (——) and estimates (mean±s.d.) per time point (–•–•–)
Figure 4
Figure 4
Observed (mean±s.d.) and predicted (mean) profiles of sorbitol plasma concentration for the octreotide (•) and somatostatin (○) and placebo (□) treatment
Figure 5
Figure 5
Top panel: predicted (mean±s.d.) profiles of sorbitol plasma clearance for the octreotide (•) and somatostatin (○) treatment. Bottom panel: observed (mean±s.d.) echo-Doppler measured flow in the right portal vein for the octreotide (•) and somatostatin (○) treatment
See this image and copyright information in PMC

References

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