Selegiline pharmacokinetics

Kivisto KT, Wang JS, Backman JT, Nyman L, Taavitsainen P, Anttila M, Neuvonen PJ. Selegiline pharmacokinetics are unaffected by the CYP3A4 inhibitor itraconazole. Eur J Clin Pharmacol 2001 57(1) 37 2. 

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. 

A comparison of the pharmacokinetics of selegiline in 14 male patients (18 to 30 years of age) with 6 elderly male patients (age > 60 years) indicated that the Cmm and the AUC remains unaltered between the young and the elderly patients. The tm of selegiline in the elderly patients was almost twofold longer than in the young patients (3.2 h in the elderly patients vs. 1.5 h in the young) however, because of the small sample size and high variability in tm p, this difference may not be a real difference and may not have any clinical impact. 

Desmethylselegiline is also an irreversible inhibitor of monoamine oxidase B in humans. There is evidence that the 1-stereoisomers of 1-amphetamine and 1-methamphetamine may have some qualitatively different actions from their d-isomer counterparts, which might result in beneficial clinical effects and could complement any beneficial clinical actions of selegiline itself. Food has no effect on the pharmacokinetics of desmethylselegiline, methamphetamine, and amphetamine. At a dose of 10 mg per day, selegiline is devoid of the cheese effect that is, it does not cause hypertension when taken with tyramine-containing foods such as cheese. 

After a 5-week washout, the 12 subjects who took citalopram in the first part of the study received 10 mg of selegiline once daily for 4 d to compare the pharmacokinetics of selegiline with and without concomitant citalopram. The safety analysis showed no significant differences in vital signs or the frequency of adverse events between the study groups. Plasma prolactin concentrations... 

Transdermai administration of high doses of selegiline may improve the pharmacokinetic and active metabolite profile of this drug s use as an antidepressant... 

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. 

Heinonen E, Anttila M, Lammintausta A. Pharmacokinetic aspects of 1-deprenyl (selegiline) and its metabolites. Clin Pharmacol Ther 1994 56 742-749. 

Selegiline, catechol-O-methyl-transferase (COMT) inhibitors, and control led-release carbidopaA-dopa decrease response fluctuations through pharmacokinetic mechanisms. 

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. ... 

Selegiline on the other hand had no effect on the pharmacokinetics of zolmitriptan or its metabolites, apart from a small (7%) reduction in its renal clearance. This finding was expected, since selegiline is specific for monoamine oxidase B (but note that this specificity is lost at higher doses). No special precautions would therefore seem to be necessary if selegiline is given with sumatriptan. 

Roberts J, Waller DG, O Shea N, Macklin BS, Renwick AG. The effect of selegiline on the peripheral pharmacokinetics of levodopa in young volunteers. BrJ Clin Pharmacol (1995) 40, 404-6. 

Dingemanse J,KneerJ, WaUnofer A, KettlerR,ZurcherG, Koulu M, Korn A. Pharmacokinetic-pharmacodynamic interactions between two selective monoamine oxidase inhibitors moclobemide and selegiline. Clin Neuropharmacol (1996) 19, 399-414. 

No significant pharmacokinetic interaction occurs between selegiline and cabei oline, pramipexole or ropinirole. 

No pharmacokinetic interaction was found to occur between cabergoline 1 mg daily and selegiline 10 mg daily after 22 days of concurrent use in a study in 6 subjects with Parkinson s disease. ... 

The manufacturers of pramipexole say that no pharmacokinetic interaction occurs with selegiline. ... 

The manufacturers of ropinirole note that a population pharmacokinetic analysis showed a lack of effect of selegiline on ropinirole. ... 

The concurrent use of selegiline and itraconazole does not appear to alter the pharmacokinetics of either drug. 

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