title: Using the fish plasma model for comparative hazard identification for pharmaceuticals in the environment by extrapolation from human therapeutic data.
abstract: Thousands of drugs are currently in use, but only for a few of them experimental chronic fish data exist. Therefore, Huggett et al. (Human Ecol Risk Assess 2003; 9:1789-1799) proposed the fish plasma model (FPM) to extrapolate the potential of unintended long-term effects in fish. The FPM compares human therapeutic plasma concentrations (HPC(T)) with estimated fish steady-state concentrations (FPC(ss)), under the assumption that biological drug targets may be conserved across the species. In this study, the influence of using different input parameters on the model result was characterised for 42 drugs. The existence of structurally and functionally conserved protein targets in zebrafish could not be refuted. Thus, the FPM model application was not in contradiction to its basic assumption. Further, dissociation of drugs was shown to be important in determining the output and model robustness. As the proposed model for FPC(ss) estimation was considered to predict accurate values for neutral and lipophilic chemicals only, a modified bioconcentration model was used with D(OW) as predictor. Using reasonable worst case assumptions, a hazard was indicated for one third of the selected drugs. Our results support the notion that this approach might help to prioritise among in use drugs to identify compounds where follow up evidence should be considered.
authors: UFZ-Helmholtz Centre for Environmental Research, Department Bioanalytical Ecotoxicology, Permoserstrasse 15, 04318 Leipzig, Germany.
authors: René
authors: R
authors: Schreiber
authors: Ulrike
authors: U
authors: Gündel
authors: Stephanie
authors: S
authors: Franz
authors: Anette
authors: A
authors: Küster
authors: Bettina
authors: B
authors: Rechenberg
authors: Rolf
authors: R
authors: Altenburger
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000097:blood* / Q000378:metabolism; D010599:Pharmacokinetics; D011506:Proteins / Q000378:metabolism; D018570:Risk Assessment / Q000379:methods; D014867:Water / Q000737:chemistry; D015027:Zebrafish
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins; D014867:Water; D020003:1-Octanol