Wikell Cecilia, Eap Chin B, Josefsson Martin, Apelqvist Gustav, Ahlner Johan, Baumann Pierre, Bengtsson Finn
Department of Clinical Pharmacology, Lund University, Lund, Sweden.
Chirality. 2002 May 5;14(4):347-50. doi: 10.1002/chir.10088.
Portacaval shunted (PCS) rats, a model of hepatic encephalopathy, and control animals were administered racemic venlafaxine for 14 days (10 mg/kg). The levels of the S- and R-enantiomers and the S/R-enantiomer ratios of venlafaxine and its metabolites were assessed by an enantiomer-selective chromatographic assay in serum, brain parenchyma, and brain dialysate of both groups. Higher levels of the S- and R-enantiomers of venlafaxine were found in serum and brain of PCS vs. normal rats (median values of S- and R-venlafaxine in serum: 290 and 201 nM in PCS; 97 and 66 nM in normal rats; median values of S- and R-venlafaxine in cortex: 956 and 939 nM in PCS; 357 and 318 nM in normal rats). Interestingly, similar S/R-venlafaxine ratios were observed in PCS and normal rats both in serum (S/R = 1.4) and brain compartments (S/R = l.0-1.1). These findings may have clinical relevance for the safety of venlafaxine in chronic hepatic encephalopathy.
将患有肝性脑病的门腔分流（PCS）大鼠模型和对照动物给予消旋文拉法辛14天（10mg/kg）。通过对两组动物的血清、脑实质和脑透析液进行对映体选择性色谱分析，评估文拉法辛及其代谢产物的S-和R-对映体水平以及S/R对映体比率。与正常大鼠相比，PCS大鼠血清和脑中的文拉法辛S-和R-对映体水平更高（血清中S-和R-文拉法辛的中位数：PCS大鼠为290和201nM；正常大鼠为97和66nM；皮层中S-和R-文拉法辛的中位数：PCS大鼠为956和939nM；正常大鼠为357和318nM）。有趣的是，在PCS大鼠和正常大鼠的血清（S/R = 1.4）和脑区室（S/R = 1.0 - 1.1）中观察到相似的S/R-文拉法辛比率。这些发现可能对文拉法辛在慢性肝性脑病中的安全性具有临床意义。
