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Exposure via biotransformation: Oxazepam reaches predicted pharmacological effect levels in European perch after exposure to temazepam

Cerveny, Daniel and Fick, Jerker and Klaminder, Jonatan and Bertram, Michael and Brodin, Tomas (2021). Exposure via biotransformation: Oxazepam reaches predicted pharmacological effect levels in European perch after exposure to temazepam. Ecotoxicology and Environmental Safety. 217 , 112246
[Research article]

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Abstract

It is generally expected that biotransformation and excretion of pharmaceuticals occurs similarly in fish and mammals, despite significant physiological differences. Here, we exposed European perch (Perca fluviatilis) to the benzodiazepine drug temazepam at a nominal concentration of 2 µg L−1 for 10 days. We collected samples of blood plasma, muscle, and brain in a time-dependent manner to assess its bioconcentration, biotransformation, and elimination over another 10 days of depuration in clean water. We observed rapid pharmacokinetics of temazepam during both the exposure and depuration periods. The steady state was reached within 24 h of exposure in most individuals, as was complete elimination of temazepam from tissues during depuration. Further, the biologically active metabolite oxazepam was produced via fish biotransformation, and accumulated significantly throughout the exposure period. In contrast to human patients, where a negligible amount of oxazepam is created by temazepam biotransformation, we observed a continuous increase of oxazepam concentrations in all fish tissues throughout exposure. Indeed, oxazepam accumulated more than its parent compound, did not reach a steady state during the exposure period, and was not completely eliminated even after 10 days of depuration, highlighting the importance of considering environmental hazards posed by pharmaceutical metabolites.

Authors/Creators:Cerveny, Daniel and Fick, Jerker and Klaminder, Jonatan and Bertram, Michael and Brodin, Tomas
Title:Exposure via biotransformation: Oxazepam reaches predicted pharmacological effect levels in European perch after exposure to temazepam
Series Name/Journal:Ecotoxicology and Environmental Safety
Year of publishing :2021
Volume:217
Article number:112246
Number of Pages:6
ISSN:0147-6513
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 401 Agricultural, Forestry and Fisheries > Fish and Aquacultural Science
Keywords:metabolic transformation, metabolite, pharmaceutical, psychoactive drug, fish, accumulation, depuration
URN:NBN:urn:nbn:se:slu:epsilon-p-111726
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-111726
Additional ID:
Type of IDID
DOI10.1016/j.ecoenv.2021.112246
ID Code:23749
Faculty:S - Faculty of Forest Sciences
Department:(S) > Dept. of Wildlife, Fish and Environmental Studies
Deposited By: SLUpub Connector
Deposited On:24 May 2021 12:03
Metadata Last Modified:24 May 2021 12:11

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