Posted by Ktemene on September 14, 2005, at 6:23:57
In reply to Re: selegiline, poop out?, posted by mogger on September 7, 2005, at 0:54:34
Hi Mogger,
I'm with Declan on dosage experience with selegiline. I take low dose selegiline (5mg every morning with 500mg DLPA + 150mg Wellbutrin) and I have never taken a higher dose of selegiline than that. But most people do not get a good effect from low dose selegiline (although several people on this board have reported that low dose selegiline helped them a lot). There was a Current Psychiatry article in 2002 (Vol. 1, No.6 /June 2002) that reported that the dose to aim for when starting selegiline is 45mg per day, and if the response is not what one hoped for, then the dose can be increased. The URL for the article is here: http://www.currentpsychiatry.com/2002_06/06_02_maoi.asp
There is another informative article about MAOI's that discusses deprenyl (selegiline) called "Monoamine Oxidase: Basic and Clinical Perspectives" at http://www.acnp.com/G4/GN401000046/CH046.html
I hope your sister is feeling better soon.
Ktemene
P.S. By the way, some people think that they get a better effect from selegiline if they open the capsule, pour the selegiline hydrochloride powder into their mouths and wait a few minutes before they swallow. I know Larry Hoover took selegiline this way, and I have been taking my 5mg selegiline this way every morning. (The taste is not great, and it makes my mouth feel numb for a few minutes.) A version of selegiline was developed to take advantage of the fact that selegiline can be absorbed directly through the tissues inside the mouth. I have coped a short article about it below.
Comment in:
* J Neural Transm. 2003 Nov;110(11):1273-8.
A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition.
Clarke A, Brewer F, Johnson ES, Mallard N, Hartig F, Taylor S, Corn TH.
Scherer DDS, Swindon, United Kingdom. aclarke@cephalon.com
Seven randomised comparative studies were conducted in healthy volunteers to compare the pharmacokinetic and pharmacodynamic profiles of selegiline hydrochloride in a new formulation designed for buccal absorption "Zydis Selegiline" (1.25-10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg). A total of 156 healthy volunteers participated in these studies. Plasma concentrations of selegiline and its primary metabolites, N-desmethylselegiline (DMS), l-amphetamine (AMT), and l-methamphetamine (MET) were measured using Gas Chromatography Mass Spectrometry (GCMS) and gas liquid chromatography (GLC) assays. Inhibition of monoamine-oxidase type B (MAO-B) and monoamine oxidase type A (MAO-A) activity was determined by measurement of as beta-phenylethylamine (PEA) by GCMS and 5-hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) assays. Almost a third (2.96 mg) of a 10 mg selegiline dose in Zydis Selegiline was absorbed pre-gastrically (predominantly buccally) within 1 minute. Mean [SD] area-under-the curve (AUC(0- infinity)) values following Zydis Selegiline 10 mg (5.85 [7.31] ng.h/mL) were approximately five times higher than those following conventional selegiline tablets 10 mg (1.16 [1.05] ng.h/mL). In contrast, plasma concentrations of metabolites were significantly ( p<0.001) lower following Zydis Selegiline 10 mg than following conventional selegiline tablets 10 mg. Plasma concentrations of selegiline and its metabolites increased in a dose-dependent manner over the dose-range Zydis Selegiline 1.25-5 mg. Bioavailability was determined using AUC and peak plasma concentrations (C(max)). The C(max) of selegiline was similar following administration of Zydis Selegiline 1.25 mg (1.52 ng/mL) or conventional selegiline tablets 10 mg (1.14 mg/mL). The range of values for AUC(0- infinity) and C(max) following Zydis Selegiline 1.25 mg were entirely contained within the range following conventional selegiline tablets 10 mg, with a much higher variability of plasma selegiline concentrations occurring after conventional selegiline tablets than after Zydis Selegiline. As expected, peak plasma concentrations for DMS, AMT and MET were consistently lower after Zydis Selegiline 1.25 mg (1.19, 0.34, 0.93 ng/ml, respectively) than after conventional selegiline tablets 10 mg (18.37, 3.60, 12.92 ng/ml, respectively). A significant (r=0.0001) correlation between daily PEA excretion (a measure of brain MAO-B inhibition) and the log-transformed AUC((0-t)) for selegiline was demonstrated. Mean daily PEA excretion was similar following Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg (13.0 microg versus 17.6 microg). In contrast, there was no correlation between PEA excretion and selegiline metabolites, indicating that selegiline metabolites do not significantly inhibit MAO-B. Urinary excretion of 5-HIAA (used as a marker for MAO-A inhibition) was unrelated to plasma concentrations of selegiline or DMS following single or repeat dosing of Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg. However, comparison of treatment groups revealed a significantly lower excretion of 5-HIAA in the conventional selegiline tablets 10 mg group than in the Zydis Selegiline 1.25 mg group after repeated administration over 13 days. In summary, by reducing the opportunity for first-pass metabolism, the absorption of selegiline from Zydis Selegiline was more efficient and less variable than from conventional selegiline tablets. Compared with conventional selegiline tablets 10 mg, Zydis Selegiline 1.25 mg yielded similar plasma concentrations of selegiline and degree of MAO-B inhibition, but markedly reduced concentrations of the principal metabolites. Thus, the lower but equally MAO-B inhibitory dose of selegiline in Zydis Selegiline 1.25 mg, which is associated with lower concentrations of potentially harmful metabolites, could offer a safer and more predictable treatment in the management of patients with Parkinson's disease.
Publication Types:
* Clinical Trial
* Randomized Controlled Trial
PMID: 14628189 [PubMed - indexed for MEDLINE]
poster:Ktemene
thread:550825
URL: http://www.dr-bob.org/babble/alter/20050812/msgs/554919.html