Single oral dose studies do not predict multiple dose kinetics, however. At steady state the peak plasma level of selegiline is 4 fold that obtained following a single dose. Metabolite concentrations increase to a lesser extent, averaging 2 fold that seen after a single dose.

The bioavailability of selegiline is increased 3 to 4 fold when it is taken with food.

The extent of systemic exposure to selegiline at a given dose varies considerably among individuals. Estimates of systemic clearance of selegiline are not available. Following a single oral dose, the mean elimination half-life of selegiline is two hours. Under steady state conditions the elimination half-life increases to ten hours.

Because selegiline's inhibition of MAO-B is irreversible, it is impossible to predict the extent of MAO-B inhibition from steady state plasma levels. For the same reason, it is not possible to predict the rate of recovery of MAO-B activity as a function of plasma levels. The recovery of MAO-B activity is a function of de novo protein synthesis; however, information about the rate of de novo protein synthesis is not yet available. Although platelet MAO-B activity returns to the normal range within 5 to 7 days of selegiline discontinuation, the linkage between platelet and brain MAO-B inhibition is not fully understood nor is the relationship of MAO-B inhibition to the clinical effect established (see Clinical Pharmacology).

Special Populations

Renal Impairment

No pharmacokinetic information is available on selegiline or its metabolites in renally impaired subjects.

Hepatic Impairment

No pharmacokinetic information is available on selegiline or its metabolites in hepatically impaired subjects.

Age

Although a general conclusion about the effects of age on the pharmacokinetics of selegiline is not warranted because of the size of the sample evaluated (12 subjects greater than 60 years of age, 12 subjects between the ages of 18 to 30), systemic exposure was about twice as great in older as compared to a younger population given a single oral dose of 10 mg.

Gender

No information is available on the effects of gender on the pharmacokinetics of selegiline.

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