| RESEARCH ARTICLE
|Year : 2012 | Volume
| Issue : 1 | Page : 20-25
Pharmacokinetics of venlafaxine and its major metabolite o-desmethylvenlafaxine in freely moving mice using automated dosing/sampling system
Bijay Aryal1, Dipendra Aryal1, Eun-Joo Kim2, Hyung-Gun Kim1
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
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.
Department of Pharmacology, College of Medicine, Dankook University, San#29, Anseo-dong, Dongnam-gu Cheonan, Choongnam
Republic of Korea
Source of Support: Grant from institute of Bio-Science and Technology (IBST) at Dankook University in 2009., Conflict of Interest: None
[FULL TEXT] [PDF]*