Trout and Human Plasma Protein Binding of Selected Pharmaceuticals informs the Fish Plasma Model

Environmental Toxicology and Chemistry
Luise HennebergerBeate Escher

Abstract

Concerns are increasing that pharmaceuticals released into the environment pose a risk to non-target organism like fish. The fish plasma model (FPM) is a read-across approach and uses human therapeutic blood plasma concentrations for estimating likely effects in fish. However, the FPM neglects differences in plasma protein binding between fish and humans. Since binding data for fish plasma are scarce, the binding of twelve active pharmaceutical ingredients (APIs, acidic, basic and neutral) to rainbow trout (Oncorhynchus mykiss) and human plasma was measured using solid-phase microextraction (SPME). The plasma-water distribution ratios (Dplasma/w ) of neutral and basic APIs were similar for trout and human plasma, differing by not more than a factor of 2.7 per API. For the acidic APIs Dplasma/w of trout plasma were much lower than for human plasma, by up to a factor of 71 for naproxen. The lower affinity of the acidic APIs to trout plasma compared to human plasma suggests that the bioavailability of these APIs is higher in trout. Read-across approaches like the FPM should account for differences in plasma protein binding to avoid over- or underestimation of effects in fish. For the acidic APIs, the effect ratio of the FPM would ...Continue Reading

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