Pharmacokinetics and Absolute Bioavailability of Selegiline Following Treatment of Healthy Subjects With the Selegiline Transdermal System (6 mg/24 h): A Comparison With Oral Selegiline Capsules

Abstract

The selegiline transdermal system is a monoamine oxidase inhibitor that was recently approved by the US Food and Drug Administration for the treatment of major depressive disorder. The current study was conducted during the selegiline transdermal system development program to characterize the single-dose pharmacokinetics and absolute bioavailability of selegiline administered by the 6-mg/24-h selegiline transdermal system in healthy volunteers. Selegiline transdermal system results were compared with those obtained after a single 10-mg oral dose of selegiline HCl. The selegiline pharmacokinetics differed greatly between the 2 routes of administration. Transdermal selegiline administration reduced metabolism and produced a high, sustained plasma selegiline concentration over the dosing period, with an absolute bioavailability of 73%. By contrast, oral dosing produced a sharp plasma selegiline peak that occurred within 1 hour and declined rapidly, with an absolute bioavailability of 4%. The data provide the basis for therapeutic advantages of the selegiline transdermal system in administering antidepressant doses of selegiline.

Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats

“…2, the trough concentration range after oral administration was wider than after patch administration, which may be associated with the gastrointestinal tract (effects of pH, motility, transit time and food intake). According to previous reports [16][17][18][19], interindividual variation (mean CV) of C max after patch administration was generally smaller than that after oral administration. In the multiple-dose study, the CV of C max after patch administration was smaller than oral administration (oral versus patch administration, 54.92 versus 13.33%).…”

Kinetic Modeling of the Monoamine Oxidase B Radioligand [11C]SL25.1188 in Human Brain with High-Resolution Positron Emission Tomography

“…These radioligands are irreversible and selective for MAO-B. However, they have metabolites (R( À ) methamphetamine and R( À ) amphetamine) 9,10 that are brain penetrant, bind specifically to monoamine transporters, which may influence the time-activity curves (TACs) from which parameters related to MAO-B activity are derived. [ 11 C]L-deprenyl-D2 represents an improvement on [ 11 C]Ldeprenyl as it reduces the rate of trapping of radioligand improving the sensitivity to changes in MAO-B activity.…”

R-Deprenyl: Pharmacological Spectrum of its Activity

“…R-deprenyl has considerable first pass metabolism [4,28,52,54,56], the biological availability was found 4% in humans [2]. Concomitant food consumption has increased the absorbed amount of R-deprenyl by about three times, without changing the plasma concentration of its metabolites [5].…”