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The Pharmacokinetics of Venlafaxine When Given in a Twice‐Daily Regimen
Author(s) -
Troy Steven M.,
Parker Ver D.,
Fruncillo Richard J.,
Chiang Soong T.
Publication year - 1995
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1995.tb04081.x
Subject(s) - venlafaxine , cmax , pharmacokinetics , active metabolite , bioequivalence , pharmacology , regimen , confidence interval , venlafaxine hydrochloride , bioavailability , crossover study , medicine , cyp2d6 , area under the curve , metabolite , antidepressant , alternative medicine , pathology , cytochrome p450 , metabolism , hippocampus , placebo
The comparative bioavailability of the novel antidepressant venlafaxine and its pharmacologically active metabolite O‐desmethylvenlafaxine was assessed when venlafaxine was given orally twice daily (75 mg bid) or 3 times daily (50 mg tid). Eighteen healthy subjects participated in an open‐label, randomized, two‐period, crossover study lasting 12 days. Each subject was randomly assigned to take venlafaxine according to a bid or a tid regimen through day 8 and was crossed over to the other regimen on days 9 to 12. The daily dose was titrated up to 150 mg/d and was held constant on days 5 to 12. Plasma samples for quantitation of venlafaxine and O‐desmethylvenlafaxine were obtained during a 24‐hour steady‐state interval on days 8 and 12. Analysis of variance showed no significant differences between the two venlafaxine regimens for peak concentration (C max ), area under the curve during 24 hours (AUC 0–24 ), trough concentration, or fluctuation ratio for venlafaxine or O‐desmethylvenlafaxine in plasma. The bioequivalence ratios for C max and AUC 0–24 of both compounds were calculated to compare the bid regimen and the tid regimen. The mean value for each of the 4 ratios was between 96 and 100%, and the 90% confidence limits around each ratio were within 90 to 110%. These results indicate that dividing a daily 150‐mg venlafaxine dose into 2 or 3 doses provides equivalent total exposure and peak plasma concentrations of venlafaxine and O‐desmethylvenlafaxine, its active metabolite. Therefore, based on pharmacokinetic considerations, it appears that the same daily dose of venlafaxine can be given in either two or three divided doses without compromising efficacy.