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Frankel, 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.


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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

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 by Altostrata
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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 

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  • 2 weeks later...

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 

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Share on other sites
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