Cost-effective pharmaceutical implants in fish: validating the performance of slow-release implants for the antidepressant fluoxetine.

Internal, slow-release implants can be an effective way to manipulate animal physiology or deliver a chemical exposure over long periods of time without the need for an exogenous exposure route. Slow-release implants involve dissolving a compound in a lipid-based carrier, which is inserted into the body of an organism. However, the release kinetics of the compound from the implant to body tissues also requires careful validation. Here, we tested and validated a slow-release implant methodology for exposing fish to a pharmaceutical pollutant, fluoxetine. We tested two lipid-based carriers (coconut oil or vegetable shortening) in the common roach (Rutilus rutilus). The implants contained either a high (50 μg/g), low (25 μg/g), or control (0 μg/g) concentration of fluoxetine, and we measured tissue uptake in the brain, muscle, and plasma of implanted fish over 25 days. The two carriers released fluoxetine differently over time: coconut oil released fluoxetine in an accelerating manner (tissue uptake displayed positive quadratic curvature), while vegetable shortening released fluoxetine in a decelerating manner (negative quadradic curvature). For both carrier types, fluoxetine was measured at the highest concentration in the brain, followed by muscle and plasma. We showed that the implants delivered an internal exposure that would be similar to if fish were exposed in surface waters containing effluents by comparing the implant exposures to waterborne exposures in the published literature. Overall, we show that slow-release internal implants are an effective method for delivering chronic exposures of fluoxetine over at least one-month timescales. Internal exposures can be an especially powerful experimental tool when coupled with field-based study designs to assess the impacts of pharmaceutical pollutants in complex, natural environments. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2023;00:0-0. © 2023 SETAC.