Enantiospecific Uptake and Depuration Kinetics of Chiral Metoprolol and Venlafaxine in Marine Medaka (Oryzias melastigma): Tissue Distribution and Metabolite Formation
- Linjie JinLinjie JinState Key Laboratory of Marine Pollution (SKLMP), and Department of Chemistry, City University of Hong Kong, Kowloon 999077, Hong Kong SAR, ChinaMore by Linjie Jin
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- Qi WangQi WangState Key Laboratory of Marine Pollution (SKLMP), and Department of Chemistry, City University of Hong Kong, Kowloon 999077, Hong Kong SAR, ChinaResearch Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, ChinaMore by Qi Wang
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- Meng YanMeng YanState Key Laboratory of Marine Pollution (SKLMP), and Department of Chemistry, City University of Hong Kong, Kowloon 999077, Hong Kong SAR, ChinaResearch Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, ChinaMore by Meng Yan
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- Jiarui GuJiarui GuState Key Laboratory of Marine Pollution (SKLMP), and Department of Chemistry, City University of Hong Kong, Kowloon 999077, Hong Kong SAR, ChinaMore by Jiarui Gu
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- Kai Zhang*Kai Zhang*Email: [email protected], [email protected]. Tel: +853 8897 1758. Fax: +853 2882 3280.National Observation and Research Station of Coastal Ecological Environments in Macao, Macao Environmental Research Institute, Macau University of Science and Technology, Taipa 999078, Macao SAR, ChinaMore by Kai Zhang
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- Paul K. S. LamPaul K. S. LamSouthern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, ChinaDepartment of Science, School of Science and Technology, Hong Kong Metropolitan University, Kowloon 999077, Hong Kong SAR, ChinaMore by Paul K. S. Lam
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- Yuefei Ruan*Yuefei Ruan*Email: [email protected], [email protected]. Tel: + 852 3442-7833. Fax: + 852 3442-0524.State Key Laboratory of Marine Pollution (SKLMP), and Department of Chemistry, City University of Hong Kong, Kowloon 999077, Hong Kong SAR, ChinaResearch Centre for the Oceans and Human Health, City University of Hong Kong Shenzhen Research Institute, Shenzhen 518057, ChinaSouthern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519000, ChinaMore by Yuefei Ruan
Abstract
The increasing use of chiral pharmaceuticals has led to their widespread presence in the environment. However, their toxicokinetics have rarely been reported. Therefore, the tissue-specific uptake and depuration kinetics of two pairs of pharmaceutical enantiomers, S-(−)-metoprolol versus R-(+)-metoprolol and S-(+)-venlafaxine versus R-(−)-venlafaxine, were studied in marine medaka (Oryzias melastigma) during a 28-day exposure and 14-day clearance period. The toxicokinetics of the studied pharmaceuticals, including uptake and depuration rate constants, depuration half-life (t1/2), and bioconcentration factor (BCF), were reported for the first time. The whole-fish results demonstrated a higher S- than R-venlafaxine bioaccumulation potential, whereas no significant difference was observed between S- and R-metoprolol. O-desmethyl-metoprolol (ODM) and α-hydroxy-metoprolol (AHM) were the main metoprolol metabolites identified by suspect screening, and the ratios of ODM to AHM were 3.08 and 1.35 for S- and R-metoprolol, respectively. N,O-Didesmethyl-venlafaxine (NODDV) and N-desmethyl-venlafaxine (NDV) were the main venlafaxine metabolites, and the ratios of NODDV to NDV were 1.55 and 0.73 for S- and R-venlafaxine, respectively. The highest tissue-specific BCFs of the four enantiomers were all found in the eyes, meriting in-depth investigation.
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