Steady-state concentration of venlafaxine enantiomers: model-based analysis of between-patient variability

To investigate patients treated for depression with respect to steady-state concentration of venlafaxine enantiomers, to quantify within- and between-subject variability and to study the possible influence of individual characteristics such as gender and age. Thirty-five inpatients received venlafax...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2002-08, Vol.58 (5), p.323-331
Main Authors: GEX-FABRY, Marianne, RUDAZ, Serge, BALANT-GORGIA, Androniki E, BRACHET, Anne, VEUTHEY, Jean-Luc, BALANT, Luc P, BERTSCHY, Gilles
Format: Article
Language:English
Subjects:
Adult
Age Factors
Antidepressive Agents, Second-Generation - blood
Antidepressive Agents, Second-Generation - chemistry
Antidepressive Agents, Second-Generation - pharmacokinetics
Biological and medical sciences
Cyclohexanols - blood
Cyclohexanols - chemistry
Cyclohexanols - pharmacokinetics
Desvenlafaxine Succinate
Drug Interactions
Female
Humans
Male
Medical sciences
Middle Aged
Neuropharmacology
Pharmacology. Drug treatments
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Sex Factors
Stereoisomerism
Structure-Activity Relationship
Venlafaxine Hydrochloride
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Summary:To investigate patients treated for depression with respect to steady-state concentration of venlafaxine enantiomers, to quantify within- and between-subject variability and to study the possible influence of individual characteristics such as gender and age. Thirty-five inpatients received venlafaxine orally at a fixed 300-mg daily dose. Blood samples were taken on day 14 and day 28 for therapeutic drug monitoring purposes. All measurements reflected steady-state trough values. In a first stage, plasma concentrations of racemic venlafaxine (V) and O-desmethylvenlafaxine (ODV) were measured using a gas chromatography method. In a second stage, (+)/(-) enantiomeric ratios for V and ODV were determined using a stereoselective capillary electrophoresis method. Interindividual variability was 77% and 33% for concentrations of racemic V and ODV, respectively. Intraindividual variability was below 20% for both compounds. Enantiomeric ratios did not statistically differ from unity, with median (+)/(-) ratios of 1.14 for V and 0.97 for ODV. ODV/V metabolite formation ratios for the (+) and (-) enantiomers did not significantly differ from each other (median values 2.85 and 2.37, respectively). However, reduced ODV/V ratio for the (-) enantiomer was strongly associated with decreased (+)/(-) ratio for V (r(S)=0.71, P
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-002-0473-2