Inhibition of platelet monoamine oxidase type B by selegiline.
Selegiline is an irreversible inhibitor of monoamine oxidase type B (MAO-B). No comparative data are available on the MAO-B inhibition caused by orally and intravenously administered selegiline. This study aimed to clarify this matter and to investigate the dose-response of MAO inhibition caused by orally administered selegiline. Sixteen healthy volunteers were given selegiline as a single intravenous dose (0.5 mg) and in three low oral doses (0.5 mg, 1.0 mg, and 1.5 mg) in an open-label randomized crossover trial. The MAO-B inhibition after the 0.5-mg intravenous dose was 79.6 +/- 15.1%. The dose-response of the three oral doses causing MAO-B inhibition was logistic. To check whether this equation could be applied to higher doses, eight of the volunteers were given 5-mg and 10-mg oral doses. The MAO-B inhibition after these doses (84.9 +/- 11.9% and 95.6 +/- 4.5, respectively) fitted well with the logistic model. With this equation obtained, it was calculated that a 3.4-mg oral dose of selegiline would be needed to obtain the same degree of MAO-B inhibition as after the intravenous dose of 0.5 mg. Therefore, the ratio of MAO-B inhibitory potential of intravenously and orally given selegiline is approximately 7 to 1, which fits well with the low bioavailability of the drug after oral administration.
Heinonen
E H
EH
Orion Corporation, Orion-Farmos, Turku, Finland.
Anttila
M I
MI
Nyman
L M
LM
Pyykkö
K A
KA
Vuorinen
J A
JA
Lammintausta
R A
RA
D000284:Administration, Oral; D000328:Adult; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000097:blood*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology*
D000978:Antiparkinson Agents; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D008995:Monoamine Oxidase