Cost‐Effective Pharmaceutical Implants in Fish: Validating the Performance of Slow‐Release Implants for the Antidepressant Fluoxetine

摘要

Internal, slow‐release implants can be an effective way to manipulate animal physiology or deliver a chemicalexposure over long periods of time without the need for an exogenous exposure route. Slow‐release implants involvedissolving a compound in a lipid‐based carrier, which is inserted into the body of an organism. However, the release kineticsof the compound from the implant to body tissues also requires careful validation. We tested and validated a slow‐releaseimplant methodology for exposing fish to a pharmaceutical pollutant, fluoxetine. We tested two lipid‐based carriers (coconutoil 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 ofimplanted fish over 25 days. The two carriers released fluoxetine differently over time: coconut oil released fluoxetine in anaccelerating manner (tissue uptake displayed a positive quadratic curvature), whereas vegetable shortening releasedfluoxetine in a decelerating manner (a negative quadratic curvature). For both carrier types, fluoxetine was measured at thehighest concentration in the brain, followed by muscle and plasma. By comparing the implant exposures with waterborneexposures in the published literature, we showed that the implants delivered an internal exposure that would be similar if fishwere exposed in surface waters containing effluents. Overall, we showed that slow‐release internal implants are an effectivemethod for delivering chronic exposures of fluoxetine over at least 1‐month time scales. Internal exposures can be anespecially powerful experimental tool when coupled with field‐based study designs to assess the impacts of pharmaceuticalpollutants in complex natural environments.