Characteristics of inert solute clearance by the monkey liver

Experiments were performed in the rhesus monkey to test the accuracy of the mathematical model of Wheeler and Forker, which describes the movement of inert solutes into the canaliculus, and to determine the reflection factors (σ) and diffusion permeability coefficients (K) for a variety of inert solutes (Forker EL: J Clin Invest 46:1189-1195, 1967; Forker EL: J Clin Invest 48:654-663, 1969; and Wheeler HO, Ross ED, Bradley SE: Am J Physiol 214: 866-874, 1968). [¹⁴C]Erythritol and one of [³H] inulin, [³H]sucrose, or [³H]mannitol were infused, and hepatic clearance rates measured over a large range of canalicular bile flow rates. The clearance equation of Forker and Wheeler et al. and a linear equation were fitted to data. Analysis of the relationship between bile flow and [¹⁴C]erythritol clearance rates in all 10 animals indicated again that the latter is a good measure of canalicular flow in this species. The clearance equation described the data well in the [¹⁴C]erythritol, [³H]inulin and [¹⁴C]erythritol, [³H]sucrose systems with no significant lack of fit; σ and K were resolved. The fit was significantly better than that for a straight line equation. In the [¹⁴C]erythritol, [³H]mannitol system, a straight line equation fit the data as well as the clearance equation, and K could not be resolved. Mean values for σ were 0.945 for inulin, 0.861 for sucrose, and 0.486 for mannitol. Mean values for K were 23.41 μl/min for inulin and 17.61 μl/min for sucrose. The difference between values of σ and K for sucrose and inulin was not significant. Study of the family of curves of the clearance equation revealed that resolution of the value of K should not be expected at physiologic canalicular bile flow rates when the value of a was 0.5, i.e., the data obtained in the [¹⁴C]erythritol, [³H]mannitol system did not contradict predictions of the model. It was concluded that (a) the model described by Forker and Wheeler accurately describes the clearance of inert solutes by the hepatocyte in this species, and (b) inulin is cleared mainly by diffusion and mannitol by bulk flow. Results for sucrose were less clear.