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 RESEARCH ARTICLE
Year : 2012  |  Volume : 44  |  Issue : 1  |  Page : 20-25

Pharmacokinetics of venlafaxine and its major metabolite o-desmethylvenlafaxine in freely moving mice using automated dosing/sampling system


1 Department of Pharmacology, College of Medicine, Dankook University, San#29, Anseo-dong, Dongnam-gu Cheonan, Choongnam, Republic of Korea
2 Department of Pharmacology, Korea Institute of Toxicology, 100 Jangdong, Yuseong Ku, Daejeon, Republic of Korea

Correspondence Address:
Hyung-Gun Kim
Department of Pharmacology, College of Medicine, Dankook University, San#29, Anseo-dong, Dongnam-gu Cheonan, Choongnam
Republic of Korea
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Source of Support: Grant from institute of Bio-Science and Technology (IBST) at Dankook University in 2009., Conflict of Interest: None


DOI: 10.4103/0253-7613.91861

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Objective: To assess the pharmacokinetics of venlafaxine (VEN) and its major metabolite o-desmethylvenlafaxine (ODV) in freely moving mice using automated dosing/infusion (ADI) and automated blood sampling (ABS) systems. In addition, concentration of VEN and its metabolite ODV were also measured in brain by microdialysis. Materials and Methods: Venlafaxine was administered directly via jugular vein or gastric catheterization and blood samples were collected through carotid artery. A series of samples with 10 μl of blood was collected from the mouse using ADI/ABS and analyzed with a validated LC-MS/MS system. Extracellular concentrations of VEN and ODV in brain were investigated by using microdialysis procedure. Results: The bioavailability of VEN was 11.6%. The percent AUC ratios of ODV to VEN were 18% and 39% following intravenous and intragastric administration, respectively. The terminal half-life of venlafaxine was about two hours. Extracellular concentration of VEN contributed 3.4% of the blood amount, while ODV was not detected in dialysate. Conclusion: This study suggests that besides rapid absorption of VEN, the first-pass metabolism is likely to contribute for its lower bioavailability in the mouse. The proposed automated technique can be used easily to conduct pharmacokinetic studies and is applicable to high-throughput manner in mouse model.






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