Selegiline oral

Selegiline is an irreversible but relatively selective inhibitor of MAO-B. An oral preparation is currently marketed as a treatment for Parkinson s disease. An oral dose produces meaningful inhibition of MAO-B but not MAO-A. The concept behind the transdermal patch is to preferentially deliver more selegiline to the brain than to the liver such that meaningful inhibition of both MAO-A and MAO-B is achieved in the brain but only MAO-B inhibition is achieved in the liver. The... 

No gender-related differences in the pharmacokinetics of selegiline were observed following a single oral dose of selegiline 10 mg to 6 elderly males and 6 elderly females between 60 and 85 years old. 

Disposition in the Body. Rapidly absorbed after oral administration and distributed to the tissues. Selegiline is almost completely metabolised to form methylamphetamine and amphetamine. About 50% of a dose is excreted in the urine in 24 hours and 75% in 72 hours excreted mainly as methylamphetamine with lesser amounts of amphetamine. The excretion of metabolites is increased in acid urine. About 15% of a dose is eliminated in the faeces in 72 hours. 

A fransdermal pafch for delivery of 20-40 mg/day selegiline (e.g., 20mg/20cm2) is in lafe fesfing for depression and may prove fo be a more viable freafmenf opfion for selegiline in depression fhan oral adminisfrafion... 

Major metabolite of orally administered selegiline is desmethylselegiline... 

Mascher HJ, Kikuta C, Millendorfer A, et al. Pharmacokinetics and bioequivalence of the main metabolites of selegiline desmethylselegiline, methamphetamine and amphetamine after oral administration of selegiline. Int J Clin Pharmacol Ther 1997 35 9-13. 

Azzaro, AJ. et al., Pharmacokinetics and absolute bioavailability of selegiline following treatment of healthy subjects with the selegiline transdermal system (6mg/24h) A comparison with oral selegiline capsules, J. Clin. Pharmacol., 47, 1256, 2007. 

In man, selegiline at a therapeutic oral dose of 10 mg is metabolized very quickly and is practically undetectable in plasma by currently available methods. Thus, quantitation of metabolites is often used for pharmacokinetic and comparative bioavailabilty studies. Human plasma and urinary metabolites are essentially the same as in rodents, with nor-selegiline being a minor metabolite, which therefore has failed detection in many studies. ... 

L-(-)-Selegiline is readily absorbed from the gastrointestinal tract. In humans maximum plasma levels of 33-45 ng/ml were obtained at 0.5-2 h after oral ingestion of 5... 

L-(-)-Selegiline is fairly liposoluble and thus is readily distributed in all tissues, crosses the blood brain barrier freely and concentrates there in areas rich in MAO In the plasma it is 94% bound to proteins, albumin and gamma globulins and it has a volume of distribution of some 300 liters. Its elimination tm was estimated at 39.5 23 min. Selegiline undergoes first pass metabolism in the liver after oral administration. After intravenous administration the t /2 of distribution of selegiline was about 9 min " ". ... 

In a small study, the bioavailability of selegiline was markedly higher (mean of about 20-fold) in women taking combined oral contraceptives than in those not taking contraceptives. In a controlled study, the AUC of selegiline was modestly increased by HRT (60%) and the change was not considered clinically relevant. 

It was suggested that the combined oral contraceptive inhibited the first pass metabolism of selegiline and so markedly increased its bioavailability. However, this was not found for HRT containing a different estrogenic hormone. 

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