Andie Posted December 18, 2018 Posted December 18, 2018 (edited) Frankle WG, et al. Synapse. 2018 An open-label positron emission tomography study to evaluate serotonin transporter occupancy following escalating dosing regimens of (R)-(-)-O-desmethylvenlafaxine and racemic O-desmethylvenlafaxine. Authors Frankle WG1, Robertson B2, Maier G3, Paris J4, Asmonga D4, May M4, Himes ML4, Mason NS5, Mathis CA5, Narendran R4,5. Author information 1 Department of Psychiatry, NYU Langone Medical Center, New York, New York. 2 Shire Pharmaceuticals Inc., Lexington, Massachusetts. 3 MaierMetrics and Associates, LLC, Boston, Massachusetts. 4 Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania. 5 Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania. Citation Synapse. 2018 Mar;72(3). doi: 10.1002/syn.22021. Epub 2017 Dec 13. Links https://www.ncbi.nlm.nih.gov/pubmed/29216407. Full text available here (requires membership) https://onlinelibrary.wiley.com/doi/abs/10.1002/syn.22021 Abstract SEP-227162 [R(-)-O-desmethylvenlafaxine] is an enantiomer of the venlafaxine metabolite O-desmethylvenlafaxine (ODV, Pristiq™, Wyeth). This study compared the serotonin transporter (SERT) occupancy achieved by SEP-227162 and ODV, at daily doses of 25, 50, 100, and 150 mg using [11 C]DASB positron emission tomography (PET). Sixteen healthy male subjects participated in one of four dose groups (N = 4 per group) during which they were administered two doses of the study drug (SEP-227162 or ODV). For each study drug, total daily doses of 25, 50, 100, and150 mg were studied. Subjects underwent three PET scans with [11 C]DASB. A baseline, off-medication, scan was performed prior to dosing and a [11 C]DASB PET scan was performed after 72 hr at each dose level. [11 C]DASB binding potential (BPND ) was calculated using the simplified reference tissue method. SERT occupancy was calculated as the change in BPND (ΔBPND ) from baseline scan to the on-medication scan relative to the baseline BPND value. SEP-227162 and ODV significantly reduced regional distribution volumes and region BPND values in a dose-dependent manner. Across all doses ODV produced significantly greater SERT occupancy than SEP-227162 (ANOVA F = 21.8, df = 1,23, p < .001). The total daily dose required to provide 50% SERT occupancy was 24.8 mg for SEP-227162 and 14.4 mg for ODV. In vitro data suggests a ratio of 3.3:1 for binding at human SERT for SEP-227162 relative to ODV. Our study suggests a ratio of 1.7:1, highlighting the value of in vivo imaging in the drug development process. PMID 29216407 [Indexed for MEDLINE]. Edited January 5, 2019 by Altostrata changed font Current Dose 0.5mcg Clonidine and 1.25 Diazepam PRN for treatment of iatrogenic hypertension. 2010 .Prescribed Pristiq 100 mg in July by GP 2010 .Reduced to 50mg by splitting and weighing. Held at 50mg 2014. Reduced from 50-35 .Held at 35mg. 2017. Taper from 35mg commenced using compounded Desvenlafaxine 2018. 23/06 13.5mg. 21/07 12.5mg. 25/08 11.5mg. 09/2018 10mg. 14/11 11mg (updose) 21/11 -12mg (updose) 2019. Still holding at 12mg and stuck. 2020. January 2019 Prozac Bridge-- Prozac 2.5 to 10mg and Pristiq 23rd Jan 6mg/ 27th Jan 5mg/ 28th Jan 3mg/ 30 Jan 0 Prozac 6th Feb 9.5mg. Vitamin D3 5000iu with K2 Magnesium Glycinate with Glycine and Passionflower 600mg
Andie Posted December 26, 2018 Author Posted December 26, 2018 Here is the graph https://onlinelibrary.wiley.com/toc/10982396/72/3 Current Dose 0.5mcg Clonidine and 1.25 Diazepam PRN for treatment of iatrogenic hypertension. 2010 .Prescribed Pristiq 100 mg in July by GP 2010 .Reduced to 50mg by splitting and weighing. Held at 50mg 2014. Reduced from 50-35 .Held at 35mg. 2017. Taper from 35mg commenced using compounded Desvenlafaxine 2018. 23/06 13.5mg. 21/07 12.5mg. 25/08 11.5mg. 09/2018 10mg. 14/11 11mg (updose) 21/11 -12mg (updose) 2019. Still holding at 12mg and stuck. 2020. January 2019 Prozac Bridge-- Prozac 2.5 to 10mg and Pristiq 23rd Jan 6mg/ 27th Jan 5mg/ 28th Jan 3mg/ 30 Jan 0 Prozac 6th Feb 9.5mg. Vitamin D3 5000iu with K2 Magnesium Glycinate with Glycine and Passionflower 600mg
Administrator Altostrata Posted January 5, 2019 Administrator Posted January 5, 2019 That is a very familiar slope! Why taper? SERT transporter occupancy studies show importance of gradual change in plasma concentration Thanks, Andie. This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner. "It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein All postings © copyrighted.
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