Department of Pharmacology, College of Medicine, Dankook University, San#29, Anseo-dong, Dongnam-gu Cheonan, Choongnam, Republic of Korea.
Indian J Pharmacol. 2012 Jan;44(1):20-5. doi: 10.4103/0253-7613.91861.
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.
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.
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.
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.
使用自动给药/输注（ADI）和自动采血（ABS）系统评估在自由活动的小鼠中文拉法辛（VEN）及其主要代谢物 O-去甲文拉法辛（ODV）的药代动力学。此外，还通过微透析测量了 VEN 和其代谢物 ODV 在大脑中的浓度。
文拉法辛通过颈静脉或胃管直接给药，通过颈动脉采集血样。使用 ADI/ABS 从小鼠中采集一系列 10 μl 的血样，并使用经过验证的 LC-MS/MS 系统进行分析。通过微透析程序研究了脑中外源 VEN 和 ODV 的浓度。
VEN 的生物利用度为 11.6%。静脉内和胃内给药后，ODV 与 VEN 的 AUC 比值分别为 18%和 39%。文拉法辛的终末半衰期约为 2 小时。细胞外 VEN 浓度占血液量的 3.4%，而 ODV 未在透析液中检出。
本研究表明，除了 VEN 的快速吸收外，首过代谢可能是其在小鼠中生物利用度较低的原因。所提出的自动技术可用于轻松进行药代动力学研究，并且适用于小鼠模型中的高通量方式。
