title: Distribution of intraperitoneally injected diclofenac in brown trout (Salmo trutta f. fario).
abstract: The detection of low levels of pharmaceuticals in aquatic environments has lately raised concerns regarding possible adverse effects of these highly active substances on aquatic organisms. The non-steroidal anti-inflammatory drug diclofenac (DCF) is one of the pharmaceutical substances regularly detected in surface waters and has lately been demonstrated to elicit adverse effects in salmonid species at environmentally relevant concentrations. The aim of the present study was to investigate the distribution of DCF in indigenous brown trout (Salmo trutta f. fario) following intraperitoneal (i.p.) injection of a single dose of (14)C-labelled DCF. A distribution kinetic over 36 h provides information on possible accumulation of DCF in different organs as well as on DCF detoxification in trout, possibly enabling identification of sites of preferential toxicity. Approximately 57% of the total single DCF dose appeared in the bile 6 h after i.p. application. Subsequently, DCF was observed to undergo enterohepatic cycling with an amount of (14)C-activity comparable to the 6 h bile values reappearing in bile 36 h after application. Results for (14)C-activity in intestine and pylori support the observation of enterohepatic cycling with a small peak in intestine at 3 h post i.p. injection and a low peak in intestine and pylori at 6 h post i.p. injection, reflecting presence of the drug substance in bile. The highest activity in intestine was found 24 h post-injection coinciding with low levels in bile, followed by a gradual decrease of activity in intestine mirroring the re-uptake of DCF into bile. The finding of enterohepatic cycling of DCF in brown trout is suggestive of a prolonged retention of DCF in brown trout.
authors: Human and Environmental Toxicology, University of Konstanz, 78464 Konstanz, Germany. birgit.hoeger@novartis.com
authors: Birgit
authors: B
authors: Hoeger
authors: Daniel R
authors: DR
authors: Dietrich
authors: Daniela
authors: D
authors: Schmid
authors: Andreas
authors: A
authors: Hartmann
authors: Bettina
authors: B
authors: Hitzfeld
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004350:Drug Residues / Q000032:analysis; D007263:Infusions, Parenteral; D015394:Molecular Structure; D014018:Tissue Distribution; D014337:Trout / Q000502:physiology*; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002250:Carbon Radioisotopes; D014874:Water Pollutants, Chemical; D004008:Diclofenac