Posted by OldSchool on February 20, 2002, at 9:43:16
http://www.mhsource.com/pt/p011040.html
Investigating Innovations
With reversible monoamine oxidase-A inhibitor antidepressants such as moclobemide not yet available in the United States, there is interest in the selective monoamine oxidase-B inhibitor approved for Parkinson's disease, selegiline (Eldepryl), as a possible alternative for depression with less liability than the monoamine oxidase inhibitor antidepressants for hypertensive drug interactions. A transdermal delivery system for selegiline was investigated by manufacturer Somerset Pharmaceuticals to ascertain whether circumventing the "first-pass" hepatic metabolism of oral administration and delivering higher selegiline levels to the central nervous system also reduced potential for adverse interaction with co-administered pressor drugs or with dietary tyramine.
In the first safety study, 10 healthy volunteers received the selegiline transdermal system (STS) with 20 mg/20 cm2 alone and with pseudoephedrine (Sudafed) in increasing dosage over two weeks. Tolerance of the combination was ascertained through monitoring of vital signs, electrocardiograms (EKGs), physical examinations and clinical laboratory results. Administration of the STS alone had little effect on blood pressure or heart rate, while pseudoephedrine alone raised both. Addition of pseudoephedrine to steady-state administration of STS, however, caused minimal changes in the pressor response indicators; and there were no clinically meaningful changes in other monitored parameters.
In another manufacturer-sponsored safety study, 301 patients with major depression were randomized to receive either the STS or topical placebo over an eight-week period without dietary tyramine restrictions. Safety monitoring revealed adverse effects, most of mild to moderate intensity, in 82.6% of patients with the STS and 77.6% of those with placebo; a statistically insignificant difference. There were no statistically significant differences between the groups in vital signs, physical examination, laboratory or EKG.
A separately reported kinetics study indicated that the STS provided higher and more sustained selegiline blood levels than oral administration, with significantly less metabolite formation. The researchers concluded that the transdermal administration of selegiline is safe for adults with major depression, and they anticipate future trials of efficacy.
Old School
poster:OldSchool
thread:94771
URL: http://www.dr-bob.org/babble/20020215/msgs/94771.html