venlafaxine (Effexor)
Use of vancomycin silica stationary phase in packed capillary electrochromatography. II. Enantiomer separation of venlafaxine and O-desmethylvenlafaxine in human plasma.

Fanali S, Rudaz S, Veuthey JL, Desiderio C.

Istituto di Cromatografia, Consiglio Nazionale delle Ricerche, Area della Ricerca di Roma, Rome, Italy.

A capillary electrochromatography method, using vancomycin chiral stationary phase packed capillary, was optimized for the simultaneous chiral separation of the antidepressant drug venlafaxine and its main active metabolite O-desmethylvenlafaxine. Simultaneous baseline enantiomeric separation of the two compounds was obtained using a mobile phase composed of 100 mM ammonium acetate buffer pH 6/water/acetonitrile (5:5:90, v/v). The electrokinetic injection for sample introduction provided a limit of quantitation for both the compounds of 0.05 microg/ml racemate concentration suitable for the analysis of venlafaxine and metabolite in biological samples. The acetonitrile mobile phase concentration was found to modulate the analytes elution times, the enantiomeric resolution and the efficiency of the separation. The column was tested for repeatability and linearity showing RSD values (%) in the range of 0.13-0.24, 2.47-3.66 and 1.35-2.50 for migration time, sample/internal standard peak area ratio and enantiomeric resolution, respectively and correlation coefficients higher than 0.9990. The method was applied to the analysis of clinical samples of patients under depression therapy showing a stereoselective metabolism for venlafaxine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11459304&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Postmortem tissue concentrations of venlafaxine.

Goeringer KE, McIntyre IM, Drummer OH.

Department of Forensic Medicine, Victorian Institute of Forensic Medicine, Monash University, Southbank, Australia. kabrenae vifp.monash.edu.au

Venlafaxine is a phenethylamine antidepressant which inhibits both serotonin and norepinephrine reuptake and is structurally unrelated to the serotonin reuptake inhibitors (SSRIs). Its major metabolite, O-desmethylvenlafaxine (ODV), also inhibits serotonin reuptake. Although metabolized by the cytochrome P-450 (CYP) system, venlafaxine inhibits CYP 2D6 and 3A4 to a far lesser extent than do the SSRIs. Mechanisms of drug action are reviewed and evaluated in the investigation of 12 fatalities occurring over a 6-month-period where venlafaxine was detected.Venlafaxine and ODV were identified by liquid chromatography-mass spectrometry (LC-MS) using atmospheric pressure ionization (API) electrospray in positive mode following an n-butyl chloride extraction. Postmortem tissue concentrations studied in each of 12 postmortem cases for venlafaxine and ODV, were 0.1-36 and <0.05-3.5mg/l (peripheral blood), <0.05-22 and <0.05-9.9mg/kg (liver), <0.05-10 and <0.05-1.5mg/l (vitreous), <0.05-53 and <0.05-6.8mg/l (bile), <0.05-55 and <0.05-21mg/l (urine), respectively, and 0.1-200mg of venlafaxine in the gastric contents. Venlafaxine was typically present with other drugs, including other antidepressants, alcohol, and benzodiazepines. The potential for interaction with each drug is discussed. Over the 6-month-period of this study, there were no deaths ascribed solely to venlafaxine intoxication.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11516890&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
[14C]Serotonin uptake and [O-methyl-11C]venlafaxine kinetics in porcine brain.

Smith DF, Hansen SB, Ostergaard L, Gee AD, Danielsen E, Ishizu K, Bender D, Poulsen PH, Gjedde A.

Institute for Basic Research in Psychiatry, Department of Biological Psychiatry, Aarhus University Psychiatric Hospital, 8240 Risskov, Denmark. dfsmith inet.uni2.dk

As part of our program of developing PET tracers for neuroimaging of psychotropic compounds, venlafaxine, an antidepressant drug, was evaluated. First, we measured in vitro rates of serotonin uptake in synaptosomes prepared from selected regions of porcine brain. Then, we determined the pharmacokinetics of venlafaxine, [O-methyl-11C]-labeled for PET. Synaptosomal studies showed that the active uptake of [14C]5-HT differed markedly between brain regions, with highest rates in hypothalamus, raphe region, and thalamus, and lowest rates in cortex and cerebellum. PET studies showed that the unidirectional rate of uptake of [O-methyl-11C]venlafaxine from blood to brain was highest in the hypothalamus, raphe region, thalamus and basal ganglia and lowest in the cortex and cerebellum. Under normal physiological conditions, the capillary permeability-surface area (PS) product for [O-methyl-11C]venlafaxine could not be estimated, because of complete flow-limitation of the cerebral uptake. Nevertheless, a correlation occurred between the apparent partition volume of the radiotracer and the rate of active uptake of 5-HT in selected regions of the porcine brain. During hypercapnia, limitations of blood-brain transfer were observed, giving PS-products for water that were only ca. 50% higher than those of venlafaxine. Thus, under normal physiological conditions, the rate of uptake of venlafaxine from blood into brain is completely flow-limited.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11518644&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Rapid high-performance liquid chromatographic measurement of venlafaxine and O-desmethylvenlafaxine in human plasma. Application to management of acute intoxications.

Matoga M, Pehourcq F, Titier K, Dumora F, Jarry C.

Pharmacochimie, EA 2962, Universite Bordeaux 2 Victor Segalen, France.

Venlafaxine, a second-generation antidepressant, acts by inhibition of the reuptake of presynaptic noradrenaline and serotonin. The main metabolite, O-desmethylvenlafaxine was found biologically active. For toxicological purpose, a rapid specific and accurate RP-HPLC assay was developed for the simultaneous determination of venlafaxine and O-desmethylvenlafaxine in human plasma. A linear response was observed over the concentration range 0.2-4 microg/ml. A good accuracy (<8%) was achieved for all quality controls, with intra-day and inter-day variation coefficient less than 10%. Finally, no interference was observed with other psychotic drugs encountered in acute poisoning. This rapid method (run time <10 min) was used to manage four voluntary intoxications involving venlafaxine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11530979&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Venlafaxine in the treatment of postpartum depression.

Cohen LS, Viguera AC, Bouffard SM, Nonacs RM, Morabito C, Collins MH, Ablon JS.

Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA. lcohen2 partners.org

BACKGROUND: Although postpartum depression is a highly prevalent illness, antidepressant treatment studies of postpartum depression are sparse. Incomplete recognition and treatment of puerperal illness place women at risk for chronic depression and may have adverse effects on child development. METHOD: An 8-week, flexible-dose, open study of venlafaxine (immediate release; mean dose = 162.5 mg/day) was performed in a group of 15 women who met DSM-III-R criteria for major depressive disorder with onset within the first 3 months postpartum. Patients were assessed at baseline and every 2 weeks across the study. Measurements of outcome included the 17-item Hamilton Rating Scale for Depression (HAM-D), the Kellner Symptom Questionnaire, and the Clinical Global Impressions scale (CGI). RESULTS: Despite baseline scores of depression that were particularly high, response to treatment was robust. Twelve of 15 patients experienced remission of major depression (HAM-D score < or = 7 or CGI score < or = 2). Dramatic decrease in anxiety paralleled the decrease in depression across the sample. CONCLUSION: Venlafaxine is effective in the treatment of postpartum major depression. Early identification of women who suffer from postpartum mood disturbance is critical to minimize the morbidity associated with untreated mood disturbance and the effect of depression on children and families.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11561929&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR