Troy S M, Parker V P, Hicks D R, Pollack G M, Chiang S T
Clinical Pharmacokinetics Department, Wyeth-Ayerst Research, Philadelphia, Pennsylvania 19101, USA.
J Clin Pharmacol. 1997 Oct;37(10):954-61. doi: 10.1002/j.1552-4604.1997.tb04270.x.
Venlafaxine is a unique antidepressant currently under evaluation for treatment of various affective disorders. The pharmacokinetics and relative bioavailability of venlafaxine were evaluated in healthy volunteers after oral administration. The bioavailability of 50 mg of venlafaxine as a tablet relative to a solution was determined in a two-period randomized crossover study. The rate of absorption from the gastrointestinal tract was assessed by the time to peak plasma concentration (tmax), a model-dependent calculation of the first-order absorption rate constant, and a model-independent calculation of mean residence time. The extent of absorption was assessed by peak plasma concentration (Cmax) and area under the concentration-time curve (AUC). No statistically significant differences were observed between the two formulations for either the rate or extent of absorption. Similarly, systemic concentrations of the active O-demethylated metabolite did not significantly differ after administration of the two venlafaxine formulations. AUC ratios indicated that the relative bioavailabilities of the parent drug, and formulation of metabolite were approximately 98% and 92%, respectively, for the tablet versus the solution. A separate study was conducted to examine the influence of food on venlafaxine absorption from the 50-mg tablet. A standard, medium-fat breakfast eaten immediately before drug administration delayed the tmax of venlafaxine but did not affect Cmax or AUC. Therefore the tablet formulation of venlafaxine is bioequivalent to the oral solution, and the presence of food appears to decrease the rate but not the extent of absorption of venlafaxine from the tablet formulation.
文拉法辛是一种目前正在评估用于治疗各种情感障碍的独特抗抑郁药。在健康志愿者口服给药后，对文拉法辛的药代动力学和相对生物利用度进行了评估。在一项两期随机交叉研究中，测定了50毫克文拉法辛片剂相对于溶液的生物利用度。通过达峰时间（tmax）、一级吸收速率常数的模型依赖性计算以及平均驻留时间的模型无关性计算来评估胃肠道的吸收速率。通过血浆峰浓度（Cmax）和浓度-时间曲线下面积（AUC）评估吸收程度。两种制剂在吸收速率或程度方面均未观察到统计学上的显著差异。同样，两种文拉法辛制剂给药后，活性O-去甲基代谢物的全身浓度也没有显著差异。AUC比值表明，片剂相对于溶液，母体药物和代谢物制剂的相对生物利用度分别约为98%和92%。进行了一项单独的研究，以检查食物对50毫克片剂中文拉法辛吸收的影响。给药前立即食用标准的中脂早餐会延迟文拉法辛的tmax，但不影响Cmax或AUC。因此，文拉法辛片剂制剂与口服溶液生物等效，食物的存在似乎会降低文拉法辛从片剂制剂中的吸收速率，但不会降低吸收程度。
