venlafaxine (Effexor)
High-performance liquid chromatographic method with diode array detection for identification and quantification of the eight new antidepressants and five of their active metabolites in plasma after overdose.

Titier K, Castaing N, Scotto-Gomez E, Pehourcq F, Moore N, Molimard M.

Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Segalen, Bordeaux, France. karine.titier pharmaco.u-bordeaux2.fr

A high-performance liquid chromatographic method is described for the determination of selective serotonin reuptake inhibitors (fluvoxamine, paroxetine, sertraline, fluoxetine, citalopram, mirtazapine), serotonin norepinephrine reuptake inhibitors (milnacipram, venlafaxine), a noradrenergic and specific serotoninergic antidepressant (mirtazapine), and five pharmacologically active metabolites (desmethylcitalopram, didesmethylcitalopram, norfluoxetine, O-desmethylvenlafaxine, desmethylmirtazapine). After a double-step liquid-liquid extraction, compounds are separated on a Symmetry C8 column eluted with a gradient of acetonitrile-phosphate buffer 10 mM pH 3.8 and detected at 230 nm and 290 nm. Calibration curves were linear in the range 25 to 500 ng/mL (100-2000 ng/mL for venlafaxine and its metabolite). The limit of quantification was 25 ng/mL (100 ng/mL for venlafaxine and its metabolite). For all quality controls good accuracy was achieved (93% to 99.5%) with intraday and interday variation coefficients less than 12%. This method allows simple and rapid (run time 18 min) identification and quantification of the eight new antidepressants and five of their active metabolites. This method can be used for toxicologic purpose.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14508381&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Once daily sustained release tablets of venlafaxine, a novel antidepressant.

Makhija SN, Vavia PR.

Pharmaceutical Division, Department of Chemical Technology (Autonomous), University of Mumbai, Nathalal Parikh Marg, Matunga, Mumbai-400019, India.

Venlafaxine is a unique antidepressant that differs structurally from other currently available antidepressants. Sustained release tablets of venlafaxine to be taken once daily were formulated with venlafaxine hydrochloride equivalent to 75 mg of venlafaxine base. Matrix system based on swellable as well as non-swellable polymers was selected for sustaining the drug release. Different polymers viz. hydroxypropylmethylcellulose (HPMC), cellulose acetate, Eudragit RSPO, ethylcellulose etc. were studied. Combinations of non-swellable polymers with HPMC were also tried in order to get the desired sustained release profile over a period of 16 h. The effect of drug to polymer ratio on in vitro release was studied. The marketed formulation was evaluated for different parameters such as appearance, weight variation, drug content and in vitro drug release. The optimized formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines. These were evaluated for appearance, weight variation, thickness, hardness, friability, drug content and in vitro drug release at selected time intervals. In vivo studies were carried out for the optimized formulation in 12 healthy human volunteers and the pharmacokinetic parameters were compared with the marketed one.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12084497&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Effects of acute treatment with paroxetine, citalopram and venlafaxine in vivo on noradrenaline and serotonin outflow: a microdialysis study in Swiss mice.

David DJ, Bourin M, Jego G, Przybylski C, Jolliet P, Gardier AM.

EA 3544, Lab. Neuropharmacologie, Faculte de Pharmacie, Universite Paris-Sud, Chatenay-Malabry 92296, France.

1. This study investigated whether a single administration of a range of doses (1, 4 and 8 mg kg-1, i.p.) of paroxetine, citalopram or venlafaxine may simultaneously increase extracellular levels of 5-HT ([5-HT]ext) and noradrenaline ([NA]ext) by using in vivo microdialysis in the frontal cortex (FCx) of awake, freely moving Swiss mice. 2. In vivo, paroxetine induced similar increases in cortical [5-HT]ext at the three doses tested, and induced a statistically significant increase in cortical [NA]ext at 4 and 8 mg x kg-1. Citalopram increased neither [5-HT]ext nor [NA]ext at the lowest dose, but increased both neurotransmitter levels at 4 and 8 mg x kg-1. At these doses, citalopram induced greater increases in cortical [5-HT]ext than in [NA]ext. Venlafaxine increased [5-HT]ext and [NA]ext to about 400 and 140% of the respective basal values at 8 mg kg-1. 3. Citalopram and paroxetine have the highest potency to increase cortical [5-HT]ext and [NA]ext, respectively. In addition, the rank of order of efficacy of these antidepressant drugs to increase [5-HT]ext in vivo in the FCx of mice was as follows: venlafaxine>citalopram>paroxetine, while the efficacy to increase cortical [NA]ext in mice of paroxetine and citalopram is similar, and greater than that of venlafaxine. 4. In conclusion, extracellular levels of cortical [NA]ext increase with the highest doses of the very selective SSRI citalopram, as well as with the very potent SSRI paroxetine. Surprisingly, the SNRI venlafaxine increased cortical [5-HT]ext to a greater extent rather than [NA]ext in the range of doses studied in mice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14530210&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Differential enhancement of antidepressant penetration into the brain in mice with abcb1ab (mdr1ab) P-glycoprotein gene disruption.

Uhr M, Grauer MT, Holsboer F.

Max Planck Institute of Psychiatry, Kraepelinstrasse 10, D-80804 Munich, Germany.

BACKGROUND: Mice with a genetic disruption (knockout) of the multiple drug resistance (abcb1ab) gene were used to examine the effect of the absence of the drug-transporting P-glycoprotein (P-gp) at the blood-brain barrier on the uptake of the antidepressants venlafaxine, paroxetine, mirtazapine, and doxepin and its metabolites into the brain. METHODS: One hour after subcutaneous injection of venlafaxine, paroxetine, mirtazapine, or doxepin, knockout and wildtype mice were sacrificed, and the drug concentrations in brain, spleen, kidney, liver, and plasma were measured. RESULTS: The cerebrum concentrations of doxepin, venlafaxine, and paroxetine were higher in knockout mice, demonstrating that these substances are substrates of P-gp and that abcb1ab activity at the level of the blood-brain barrier reduces the penetration of these substances into the brain. In contrast, brain distribution of mirtazapine was indistinguishable between the groups. CONCLUSIONS: The differences reported here in brain penetration of antidepressant drugs that depend on the presence of the abcb1ab gene may offer an explanation for poor or nonresponse to antidepressant treatment. Furthermore, they may be able to explain in part the discrepancies between plasma levels of an antidepressant and its clinical effects and side effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14550684&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Venlafaxine hydrochloride for the treatment of hot flashes.

Schober CE, Ansani NT.

Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213-2546, USA. schoberce msx.upmc.edu

OBJECTIVE: To review the literature evaluating venlafaxine for the treatment of hot flashes. DATA SOURCES: Clinical literature accessed through MEDLINE (1966-August 2002), PubMed, Harrison's Online, and references of reviewed articles. Key terms used were venlafaxine, Effexor, hot flashes, and vasomotor symptoms. DATA SYNTHESIS: Not all patients experiencing hot flashes are candidates for traditional hormonal therapy. Nonhormonal alternatives have long been explored, but conflicting evidence of efficacy exists. CONCLUSIONS: Venlafaxine is an effective nonhormonal alternative for relief from uncontrolled hot flashes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14565812&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR