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Marianne Gex-Fabry

Publications and source records attributed to Marianne Gex-Fabry.

16 recordsLinked to original sources
PubMed2006

Health status of returnees to Kosovo: do living conditions during asylum make a difference?

OBJECTIVE: From August 1999 to July 2001, asylum seekers who had come to Switzerland from Kosovo were repatriated. The present study aimed to assess the relationship between living conditions during asylum in Switzerland and health status among returnees. STUDY DESIGN: Cross-sectional survey of 319 ethnic Albanian families in Kosovo, selected from a list of 12900 heads of households who had received repatriation aid. METHODS: Consenting household members aged 16 years or more who had received asylum in Switzerland were interviewed during the autumn of 2001. Questions explored living conditions during asylum, present socio-economic conditions (World Bank Kosovo Poverty Assessment Survey), subjective physical and mental health [Medical Outcomes Study 36-item Short Form Health Survey (SF-36)], traumatic events (Harvard Trauma Questionnaire) and symptoms of post-traumatic stress disorder (PTSD; Mini International Neuropsychiatric Interview). RESULTS: Ninety-four per cent of selected households were located. Among the 580 participants, 25.5% suffered from PTSD and 65% lived in extreme poverty. Subjective health scores, measured by SF-36, were low, particularly for those affected by PTSD. Among living conditions in the host country, duration of stay longer than 26 weeks was associated with lower mental health scores, particularly among people with PTSD. CONCLUSIONS: Two years after the conflict, returnees had low health scores. The association between duration of stay and lower mental health scores may reflect the stress of adapting to asylum or the consequence of compulsory repatriation. This study has implications for the emerging healthcare system in Kosovo and for policies of asylum in host countries.

Adolescent↗
PubMed2006

Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors.

BACKGROUND: Drug-induced long QT syndrome is a serious adverse drug reaction. Methadone prolongs the QT interval in vitro in a dose-dependent manner. In the inpatient setting, the frequency of QT interval prolongation with methadone treatment, its dose dependence, and the importance of cofactors such as drug-drug interactions remain unknown. METHODS: We performed a systematic, retrospective study comparing active or former intravenous drug users receiving methadone and those not receiving methadone among all patients hospitalized over a 5-year period in a tertiary care hospital. A total of 167 patients receiving methadone fulfilled the inclusion criteria and were compared with a control group of 80 injection drug users not receiving methadone. In addition to methadone dose, 15 demographic, biological, and pharmacological variables were considered as potential risk factors for QT prolongation. RESULTS: Among 167 methadone maintenance patients, the prevalence of QTc prolongation to 0.50 second((1/2)) or longer was 16.2% compared with 0% in 80 control subjects. Six patients (3.6%) in the methadone group presented torsades de pointes. QTc length was weakly but significantly associated with methadone daily dose (Spearman rank correlation coefficient, 0.20; P<.01). Multivariate regression analysis allowed attribution of 31.8% of QTc variability to methadone dose, cytochrome P-450 3A4 drug-drug interactions, hypokalemia, and altered liver function. CONCLUSIONS: QT interval prolongation in methadone maintenance patients hospitalized in a tertiary care center is a frequent finding. Methadone dose, presence of cytochrome P-450 3A4 inhibitors, potassium level, and liver function contribute to QT prolongation. Long QT syndrome can occur with low doses of methadone.

Adolescent↗
PubMed2006

Impact of the life goals group therapy program for bipolar patients: an open study.

BACKGROUND: To evaluate the level of satisfaction of bipolar patients participating in the structured group Life Goals Program (LGP), as well as the impact of this psychoeducative program on mood stability, treatment compliance and relapse prevention. METHODS: Forty-five patients (30 females and 15 males) with bipolar disorder were included. Their level of satisfaction was evaluated at the end of the 6-week phase 1 of LGP and after one-year participation in phase 2 (median duration 366 days, range 68-483). The impact of the LGP was also evaluated with respect to mood stability, compliance with pharmacological treatment and ability to prevent and cope with relapse. Participants' mood was rated at study entry, end of phase 1 and end of phase 2 with the Montgomery and Asberg Depression Rating Scale (MADRS) and Bech-Rafaelsen Mania Scale. RESULTS: Thirty-six participants (80.0%) completed phase 1 and 17 entered phase 2. A majority of participants (82.4%) were very satisfied with the information delivered during phase 1. After attending phase 2, participants reported a subjective improvement in mood stability, relapse prevention strategies as well as coping with relapse. MADRS score decreased significantly between the beginning of phase 1 and end of phase 2 (p=0.016). LIMITATIONS: This is an open study and results need to be replicated in a randomized controlled trial. CONCLUSIONS: Results of this open study suggest that the life goals psychoeducative program is well perceived by bipolar patients and has a positive impact on mood stability, relapse prevention and ability to go beyond symptoms in order to reach specific goals.

Adult↗
PubMed2005

Temporal perception in velo-cardio-facial syndrome.

Temporal perception abilities refer to timing mechanisms used in daily life, such as the ability to reproduce and judge time, previously associated with the basal ganglia and the cerebellum, respectively. In individuals affected by velo-cardio-facial (VCFS), both the basal ganglia and the cerebellum have been shown to be particularly vulnerable to abnormal brain development, though related temporal perception abilities have yet to be investigated. In this study, our goal was to characterize time perception and reproduction abilities in individuals with VCFS. Compared to controls, we hypothesized that individuals with VCFS would be less accurate and show more variability when reproducing a fixed-interval series of auditory beeps; furthermore, we predicted that they would show a higher perceptive acuity threshold when discriminating between subtle time differences. Forty-two subjects with VCFS and 35 matched controls participated in temporal perception evaluations. In the reproduction of time finger-tapping task, subjects were asked to press a button in cadence with a series of fixed interval beeps, and then to hold the same tempo when the beeps stopped. Overall, the VCFS group showed less accuracy and more variability in reproduction ability when compared to controls. In the second experiment, subjects were tested on auditory and visual time perception tasks. Subjects were presented with a fixed interval stimulus and a stimulus of varying duration, and were asked to determine the longer of the two. The VCFS group required a greater discrepancy between tones to accurately discriminate the two stimuli. The results point to an alteration in temporal perception associated with VCFS. Implications of altered temporal perception abilities and their relationship to the VCFS phenotype are discussed.

Acoustic Stimulation↗
PubMed2005

Screening for bipolar disorders using a French version of the Mood Disorder Questionnaire (MDQ).

BACKGROUND: Bipolar disorders remain much too often unrecognized and subsequently inappropriately treated. This paper presents the translation into French and validation of the MDQ, a screening instrument for bipolar spectrum disorders, in an adult psychiatric sample. Modifications of its criteria for a positive screening as well as its test-retest reliability are also addressed. METHODS: A sample of 96 patients, attending outpatient treatment programs and suffering from mood disorders, completed the MDQ before being interviewed according to the mood module of the structured clinical interview for DSM-IV (SCID). They completed the MDQ a second time 1 month later, in order to examine its stability over time. RESULTS: According to the SCID interview, 54 patients were suffering from bipolar disorder and 42 from unipolar disorder. Among the bipolar sample, the MDQ identified 74.1% of them, with higher sensitivity in bipolar I (90.3%) than bipolar II (52.4%) and 90.5% specificity. Lowering the level of impairment required for positive screening led to improved sensitivity for bipolar II patients (76.2%). The French MDQ demonstrated adequate internal consistency (Cronbach alpha=0.89). Its test-retest reliability proved to be satisfactory, with a kappa coefficient of 0.79. Similar stability over a 1-month interval was obtained for bipolar type I and type II (kappa=0.75 and 0.77, respectively). LIMITATIONS: Similarly to the American version, the French MDQ has lower sensitivity for bipolar II disorders. CONCLUSIONS: The performance of the French MDQ is comparable to the one reported in the original American study conducted with a similar patient population. In a psychiatric outpatient sample, the French MDQ proves to be a feasible and reliable screening instrument.

Adolescent↗
PubMed2005

Quantification of Gd-BOPTA uptake and biliary excretion from dynamic magnetic resonance imaging in rat livers: model validation with 153Gd-BOPTA.

OBJECTIVES: We sought to develop and validate a pharmacokinetic model allowing description of the magnetic resonance (MR) signal intensity induced by the hepatobiliary contrast agent Gd-BOPTA and to quantify the overall Gd-BOPTA transport in rat liver. MATERIALS AND METHODS: MR signal intensity was recorded during the perfusion of rat livers with Gd-DTPA, an extracellular contrast agent, and Gd-BOPTA, a hepatobiliary contrast agent. Similar experiments were conducted with Gd-labeled contrast agents for quantitative measurement in liver, bile and perfusate. RESULTS: A complete 6-compartment, 8 parameter open model was first developed to describe the pharmacokinetics of the compound based on the radioactivity data analysis. Because perfusate and bile data were not available in MRI experiments, a reduced model (6-compartment, 5 parameters) was considered for the MRI data. The performance of the reduced model was tested using the radioactivity data. The reduced model successfully described the contrast agent amount in the liver and correctly predicted amounts in bile and perfusate. CONCLUSIONS: Pharmacokinetic modeling of MR signal intensity induced by Gd-BOPTA permits quantification of Gd-BOPTA uptake and biliary excretion in rat livers.

Animals↗
PubMed2005

Structural and functional brain development after hydrocortisone treatment for neonatal chronic lung disease.

OBJECTIVE: There is much concern about potential neurodevelopmental impairment after neonatal corticosteroid treatment for chronic lung disease. Dexamethasone is the corticosteroid most often used in this clinical setting, and it has been shown to impair cortical growth among preterm infants. This study evaluated long-term effects of prematurity itself and of neonatal hydrocortisone treatment on structural and functional brain development using three-dimensional MRI with advanced image-processing and neurocognitive assessments. METHODS: Sixty children born preterm, including 25 children treated with hydrocortisone and 35 children not treated with hydrocortisone, and 21 children born at term were evaluated, at a mean age of 8 years, with quantitative MRI and neurocognitive assessments (Wechsler Intelligence Scales for Children-Revised [WISC-R]). Automatic image segmentation was used to determine the tissue volumes of cerebral gray matter, white matter, and cerebrospinal fluid. In addition, the volume of the hippocampus was determined manually. WISC-R scores were recorded as mean intelligence scores at evaluation. Neonatal hydrocortisone treatment for chronic lung disease consisted of a starting dose of 5 mg/kg per day tapered over a minimum of 3 weeks. RESULTS: Cerebral gray matter volume was reduced among preterm children (regardless of hydrocortisone treatment), compared with children born at term (preterm: 649 +/- 4.4 mL; term: 666 +/- 7.3 mL). Birth weight was shown to correlate with gray matter volume at 8 years of age in the preterm group (r = 0.421). Cerebrospinal fluid volume was increased among children born preterm, compared with children born at term (preterm: 228 +/- 4.9 mL; term: 206 +/- 8.2 mL). Total hippocampal volume tended to be lower among children born preterm, with a more pronounced reduction of hippocampal volume among boys (preterm: 6.1 +/- 0.13 mL; term: 6.56 +/- 0.2 mL). The WISC-R score was lower for children born preterm, compared with children born at term (preterm: 99.4 +/- 12.4; term: 109.6 +/- 8.8). Children treated with neonatal hydrocortisone had very similar volumes of gray matter (preterm with hydrocortisone: 650 +/- 7.0 mL; preterm without hydrocortisone: 640 +/- 5.6 mL), white matter (preterm with hydrocortisone: 503 +/- 6.1 mL; preterm without hydrocortisone: 510 +/- 4.9 mL), and cerebrospinal fluid (preterm with hydrocortisone: 227 +/- 7.4 mL; preterm without hydrocortisone: 224 +/- 6.0 mL), compared with untreated infants. The hippocampal volumes were similar in the 2 groups (preterm with hydrocortisone: 5.92 +/- 0.15 mL; preterm without hydrocortisone: 5.81 +/- 0.12 mL). The WISC-R score assessments were within the normal range for both groups, with no difference between the groups (preterm with hydrocortisone: 100.8 +/- 13; preterm without hydrocortisone: 98.6 +/- 12.3). CONCLUSIONS: Prematurity is associated with mild brain structural differences that persist at 8 years of age, with associated lower scores in neurocognitive assessments. The data suggest that perinatal hydrocortisone given at the described dosage has no long-term effects on either neurostructural brain development or neurocognitive outcomes.

Anti-Inflammatory Agents↗
PubMed2004

Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone.

BACKGROUND AND OBJECTIVES: Cytochrome P450 (CYP) 3A4 is the main CYP isozyme involved in methadone metabolism. We investigated the influence of grapefruit juice, which contains inhibitors of intestinal CYP3A, on the steady-state pharmacokinetics of methadone. METHODS: For 5 days, 8 patients undergoing methadone maintenance treatment received 200 mL water or grapefruit juice 30 minutes before and again together with their daily dose of methadone. Blood sampling for R-, S-, and R,S-methadone plasma determination was performed over a 24-hour period. CYP3A activity was determined by measuring the plasma 1'-hydroxymidazolam/midazolam ratio. RESULTS: A decrease in the midazolam ratio was measured in all patients after grapefruit juice (mean +/- SD before grapefruit juice, 9.3 +/- 5.9; mean +/- SD after grapefruit juice, 3.9 +/- 1.2; P <.05). Grapefruit juice led to a mean 17% increase in the area under the curve extrapolated to 24 hours for both enantiomers of methadone (range, 3% to 29% [P <.005]; range, -4% to 37% [P <.05]; and range, 1% to 32% [P <.01]; for R-, S-, and R,S-methadone, respectively). A similar increase in peak level and decrease in apparent clearance were measured with grapefruit juice, whereas time to peak level, terminal half-life, and apparent volume during the terminal phase of R-, S-, and R,S-methadone were not affected by grapefruit juice. No symptom of overmedication was either detected by the clinical staff or reported by the patients. CONCLUSIONS: Grapefruit juice administration is associated with a modest increase in methadone bioavailability, which is not expected to endanger patients. However, it cannot be excluded that a much stronger effect may occur in some patients, and thus grapefruit juice intake is not recommended during methadone maintenance treatment, in particular in patients initiating such a treatment.

Adult↗
PubMed2004

Patients' satisfaction with hospitalization in a mixed psychiatric and somatic care unit.

A patient satisfaction survey was undertaken in a mixed psychiatric and somatic care unit. An anonymous self-report questionnaire covering setting and satisfaction with care was completed by 60 patients. Median age was 42 (range 20-64), and the majority female (63%). Main ICD-10 diagnostic categories were depressive disorders (51.7%), substance-related disorders (33%) and personality disorders (25%). Somatic comorbidity was present in 60% of patients. Overall satisfaction with care and setting was high. Higher satisfaction was significantly associated with a history of previous hospitalizations in a psychiatric hospital and with being referred to the program by a psychiatrist. These findings emphasize the perceived advantages of mixed units, such as decreased stigmatization of psychiatric inpatients and opportunity to receive adequate treatment for both physical and mental problems during a single hospital stay.

Adult↗
PubMed2004

Determinants of postconflict symptoms in Albanian Kosovars.

During the period from 1998 to 1999, more than 1 million civilians from the province of Kosovo in the Balkans were displaced as a consequence of organized violence and war. The aim of the present study was to determine the prevalence of posttraumatic stress disorder (PTSD) in a sample of the Albanian Kosovar population more than 2 years after the end of the conflict and to assess the effect of exposure to war-related events. A total of 340 households were randomly selected among 12,900 families returned from a country of asylum (Switzerland). All adults in each household were invited to participate (N = 996). The following instruments were used: the Albanian translations of the PTSD section of the Mini International Neuropsychiatric Interview and of the Medical Outcomes Study 36-Item Short Form, and a list of traumatic events adapted from the Harvard Trauma Questionnaire. The overall prevalence of PTSD was 23.5%. A strong cumulative effect of trauma was observed, with odds ratios for PTSD rising steeply with the number of events to which people were exposed. After taking into account traumatic events, multivariable analysis indicated that female gender, older age, and having left Kosovo during the conflict were significantly associated with higher frequency of PTSD, whereas significant heterogeneity among municipalities was observed. Stratified analysis for people who stayed and left the province during the war suggested that different patterns of trauma may be relevant in the two subsamples, with forced separation and isolation strongly associated with PTSD in people who stayed in Kosovo. PTSD diagnosis was also significantly associated with lower scores on all dimensions of the Medical Outcomes Study 36-Item Short Form and lower economic status. The results suggest that responding to medium-term and long-term mental health consequences of conflict is a necessary task for the global rehabilitation of health care systems in a war devastated country.

Adolescent↗
PubMed2004

Gd-BOPTA transport into rat hepatocytes: pharmacokinetic analysis of dynamic magnetic resonance images using a hollow-fiber bioreactor.

RATIONALE AND OBJECTIVES: To investigate the transport of the hepatobiliary magnetic resonance (MR) imaging contrast agent Gd-BOPTA into rat hepatocytes. MATERIALS AND METHODS: In a MR-compatible hollow-fiber bioreactor containing hepatocytes, MR signal intensity was measured over time during the perfusion of Gd-BOPTA. For comparison, the perfusion of an extracellular contrast agent (Gd-DTPA) was also studied. A compartmental pharmacokinetic model was developed to describe dynamic signal intensity-time curves. RESULTS: The dynamic signal intensity-time curves of the hepatocyte hollow-fiber bioreactor during Gd-BOPTA perfusion were adequately fitted by 2 compartmental models. Modeling permitted to discriminate between the behaviors of the extracellular contrast agent (Gd-DTPA) and the hepatobiliary contrast agent (Gd-BOPTA). It allowed the successfully quantification of the parameters involved in such differences. Gd-BOPTA uptake was saturable at high substrate concentrations. CONCLUSIONS: The transport of Gd-BOPTA into rat hepatocytes was successfully described by compartmental analysis of the signal intensity recorded over time and supported the hypothesis of a transporter-mediated uptake.

Animals↗
PubMed2003

Time course of clinical response to venlafaxine: relevance of plasma level and chirality.

OBJECTIVE: Early clinical response to antidepressant treatment is an important therapeutic goal, considering the psychological, social and economic consequences of depression. The aim of the present study was to investigate the relationship between the time course of response and the concentration of venlafaxine (V), its active metabolite O-desmethylvenlafaxine (ODV) and enantiomeric ratios V(+)/V(-) and ODV(+)/ODV(-). METHODS: Depressed inpatients ( n=35) received V orally at a fixed 300 mg daily dose. Accepted comedication included clorazepate (maximum 60 mg/day), zopiclone (maximum 15 mg/day) and low-dose trazodone (maximum 200 mg/day). Severity of depression was assessed on days 0, 4, 7, 11, 14, 21 and 28 (Montgomery and Asberg Depression Rating Scale). Blood samples were taken on day 14 and day 28 and submitted to stereoselective determination. All measurements reflected trough steady-state values. First, pattern analysis was used to provide a categorical perspective of clinical response (50% improvement from baseline depression score). Patients displaying non-response, transient response, early persistent response and delayed persistent response were compared with respect to racemic concentrations and enantiomeric ratios. Second, in a dimensional perspective, mixed-effects modelling was used to analyse severity of depression versus time curves with respect to the possible influence of concentrations and enantiomeric ratios. RESULTS: Comparison of patients with and without persistent response did not reveal any significant difference for V, ODV, V+ODV plasma levels or enantiomeric ratios. Persistent response was significantly associated with less frequent pre-study antidepressant medication and less frequent comedication with zopiclone (day 14) and clorazepate (day 28) during the study. Focus on patients with persistent response ( n=19, 54.3%) indicated that early response, first observed before day 14, was associated with significantly higher V+ODV concentration than delayed response (median 725 ng/ml versus 554 ng/ml, P=0.023). No difference was found for pre-study medication or comedication during the study. Shorter time to onset of response was significantly associated with lower V(+)/V(-) enantiomeric ratio (r(s)=0.48, P<0.05). Mixed-effects modelling of depression severity versus time curves in patients with persistent response confirmed that either higher V+ODV plasma level or lower V(+)/V(-) ratio were significantly associated with more rapid decrease of depression score (likelihood ratio tests, P=0.012 and P=0.046, respectively). CONCLUSION: Considering its modest sample size, naturalistic design and limited observation period, the present study provided preliminary indication that earlier clinical response may occur with higher V+ODV plasma level, extending previous dose-response studies. The hypothesis was also raised that exposure to a more potent noradrenergic therapeutic moiety, as reflected by a lower V(+)/V(-) ratio, may be relevant to early improvement of depression.

Adult↗
PubMed2003

A retrospective comparison of inpatients with mixed and pure depression.

Some authors advocate a broadening of the narrow concept of mixed episodes in the direction of mania leading to the concept of mixed mania, and in the direction of depression leading to the concept of mixed depression. The latter has been little investigated so far. In the present article, we retrospectively compare 49 patients with pure depression with 51 patients with mixed depression in terms of socio-demographic and clinical variables in order to contribute to the validation of the distinction between mixed and pure depression. Supporting this distinction, we observed that mixed depressive patients more frequently had past histories of bipolar disorder and alcohol abuse and had longer durations of hospital stay. These last two points remain significant even when we control for the effect of the association with bipolarity.

Adult↗
PubMed2003

Therapeutic drug monitoring of olanzapine: the combined effect of age, gender, smoking, and comedication.

Therapeutic drug monitoring (TDM) data for the antipsychotic drug olanzapine were investigated with respect to concentration versus dose relationship, intraindividual versus interindividual variability, and the combined influence of patient characteristics on steady-state concentration. The study included 250 patients, with daily doses ranging from 2.5 to 30 mg. Median concentration to dose ratio was 2.1 (ng/mL)/(mg/d), with 90% of the distribution in a fivefold range. In the first subgroup of patients with two measurements at different doses (n = 21), data were in keeping with linear concentration versus dose relationship. In the second subgroup of patients with repeated measurements at a constant daily dose (n = 40), estimates of within-patient and between-patient variabilities were 30.5% and 49.4%, respectively. In the whole sample, multiple regression analysis of dose-normalized concentration revealed significant effects of time postdose (-18% per 12 hours delay, P < 0.05), age >/=60 years (+27%, P < 0.005), cigarette smoking (-12%, P < 0.05), and comedication with fluvoxamine (+74%, P < 0.001), paroxetine, fluoxetine, or sertraline (considered together, +32%, P < 0.05), venlafaxine (+27%, P < 0.05), and inducers of P450 enzymes (-40%, P < 0.001). The final model included a tendency for higher concentration associated with female gender (+11%, P = 0.07) and accounted for 27% of observed interindividual variability. When considering a worst-case scenario, an elderly, nonsmoking woman prescribed fluvoxamine comedication was predicted to reach a 4.6-fold higher olanzapine concentration than a young male smoker coadministered carbamazepine. The current study suggests that patients characterized by a combination of factors associated with altered metabolism may benefit from olanzapine TDM.

Age Factors↗
PubMed2002

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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<0.001) and increased (+)/(-) ratio for ODV (r(S)=-0.79, P<0.001). In contrast, ODV/V ratio for the (+) enantiomer did not significantly correlate with parent compound (+)/(-) ratio and correlated only weakly with metabolite (+)/(-) ratio (r(S)=-0.38, P<0.05). When compared with males, females displayed a significantly lower ODV/V ratio for the (-) enantiomer (median values 1.42 vs 5.08 on day 14, P<0.05) but not for the (+) enantiomer (median values 2.36 vs 3.27, n.s.). Analysis did not reveal any significant association between ODV/V ratios and age, weight, height, creatinine clearance, smoking or co-medication. A pharmacokinetic model at steady state was developed that postulated two different enzyme systems to contribute to O-desmethylation. ODV(-) formation was supposed to largely depend on a single pathway, possibly impaired in a patient subpopulation. ODV(+) formation was postulated to rely on both pathways to a similar extent. Model predictions were in close agreement with observations in patients. CONCLUSION: Observations, together with model-based simulations, suggested that marked stereoselectivity in a patient subgroup may be related with impairment of O-desmethylation greater for (-) than (+) venlafaxine. This hypothesis requires testing against phenotypic and genotypic characteristics of patients.

Adult↗