Patat A, Troy S, Burke J, Trocherie S, Danjou P, Le Coz F, Allain H, Gandon J M
Biotrial Drug Evaluation and Pharmacology Research, Rennes, France.
J Clin Pharmacol. 1998 Mar;38(3):256-67. doi: 10.1002/j.1552-4604.1998.tb04423.x.
Venlafaxine is currently marketed for treatment of depressive disorders as a conventional tablet formulation with a twice or three times daily dosage regimen. The absolute bioavailability of the conventional (CF) and extended-release (XR) formulations and their effects on electroencephalograms (EEG) and on a visual analog scale (VAS) for nausea were assessed in a randomized, double-blind, four-way crossover, placebo-controlled study of 16 healthy young men who were given either a single oral dose of 50 mg of CF venlafaxine, 75 mg of XR venlafaxine, or an intravenous dose of 10 mg of venlafaxine, or a placebo at 1-week intervals. The absolute bioavailability of venlafaxine was between 40% and 45% and was similar for both the CF and XR formulations. Venlafaxine produced central effects of a desipramine-like antidepressant. Regardless of formulation tested, the main EEG changes were an increase in fast beta (20-30 Hz) energy, which was more pronounced over the frontotemporal regions and extended within the full beta range (16-40 Hz). Maximum effect was reached at 6 hours for the CF and reached a plateau from 10 to 24 hours for the XR formulation. A dose-proportional increase in central activity, expressed as area under the effect curve (AUE) of the beta band, was observed between the CF (50 mg) and XR (75 mg) formulations. Compared with the CF tablet, the XR formulation also produced a much less intense maximum effect and a decrease of 63% in the AUE of nausea normalized by dose. The XR formulation has the same absolute bioavailability and the same central activity as assessed by EEG, but produced less intensive nausea than CF venlafaxine. The present findings suggest that a once-daily dosage regimen should be sufficient. This was confirmed by several clinical trials in depressive patients.
文拉法辛目前作为一种传统片剂剂型用于治疗抑郁症，给药方案为每日两次或三次。在一项随机、双盲、四向交叉、安慰剂对照研究中，对16名健康年轻男性进行了评估，他们被给予单次口服50mg传统（CF）文拉法辛、75mg缓释（XR）文拉法辛、静脉注射10mg文拉法辛或安慰剂，给药间隔为1周，以评估传统（CF）和缓释（XR）剂型的绝对生物利用度及其对脑电图（EEG）和恶心视觉模拟量表（VAS）的影响。文拉法辛的绝对生物利用度在40%至45%之间，CF和XR剂型相似。文拉法辛产生了与地昔帕明样抗抑郁药相似的中枢作用。无论测试何种剂型，EEG的主要变化是快速β波（20 - 30Hz）能量增加，在额颞区更为明显，并在整个β波范围（16 - 40Hz）内扩展。CF剂型在6小时达到最大效应，XR剂型在10至24小时达到平台期。在CF（50mg）和XR（75mg）剂型之间观察到中枢活性呈剂量比例增加，以β波带效应曲线下面积（AUE）表示。与CF片剂相比，XR剂型产生的最大效应强度也小得多，恶心的AUE经剂量归一化后降低了63%。XR剂型具有与CF剂型相同的绝对生物利用度和通过EEG评估的相同中枢活性，但产生的恶心程度比CF文拉法辛轻。目前的研究结果表明，每日一次的给药方案应该足够。这在抑郁症患者的多项临床试验中得到了证实。
