Quantitative Cross-Species Extrapolation between Humans and Fish: The Case of the Anti-Depressant Fluoxetine
Figure 2
Fluoxetine uptake and metabolism in fathead minnow following a 28-d study.
A) Relationship between measured (red line; mean ± SD; n = 20) and predicted (dashed line) plasma concentrations of fluoxetine, based on concentrations quantified in the water. The predicted plasma concentrations were generated by using the Fish Plasma Model [18]. B) Relationship between measured plasma concentrations of fluoxetine (red line; mean ± SD; n = 20) and norfluoxetine:fluoxetine ratio (grey line, mean ± SD; n = 20). The change in the slope of the plasma concentration curve corresponds to the decrease of the norfluoxetine:fluoxetine ratio, indicating inhibitory and/or saturation effects on the metabolic enzymes that convert fluoxetine into norfluoxetine. C) Relationship between measured plasma concentrations of fluoxetine in fish plasma (mean ± SD; n = 20) and Human Therapeutic Plasma Concentration range (grey area, 91–302 ng/mL). D) Relationship between measured plasma concentrations of norfluoxetine in fish plasma (mean ± SD; n = 20) and Human Therapeutic Plasma Concentration range (grey area, 72–258 ng/mL).