Marked effect of liver and kidney function on the pharmacokinetics of selegiline.
OBJECTIVE
The pharmacokinetics of selegiline was investigated in an open study with 4 parallel groups of 10 subjects in each. Patients with liver disease, those receiving a drug that induced hepatic enzyme activity, and those with impaired kidney function were compared with control subjects.


METHODS
A single oral 20-mg dose of selegiline was administered after an overnight fast, and blood samples were collected over a period of 48 hours. Concentrations of serum selegiline and its main metabolites were determined and pharmacokinetic parameters calculated.


RESULTS
The pharmacokinetic parameters of selegiline differed considerably between the patient groups and the control subjects. The area under the concentration-time curve of serum selegiline was, on average, 18-fold higher (P < .05) in patients with impaired liver function, 23-fold lower (P < .001) in patients with drug-induced liver function, and 6-fold higher (P < .05) in patients with impaired kidney function as compared with the control subjects. There was a large interindividual variation in every group. The changes in selegiline metabolite kinetics supported the changes in the kinetics of the parent compound.


CONCLUSIONS
The elimination rate of selegiline was substantially increased in patients with drug-induced liver function and decreased in patients with impaired liver or kidney function when compared with control subjects. These results suggest that selegiline dosage adjustments may be required in patients with altered liver and kidney function.
Anttila
Markku
M
Orion Pharma, R&D, Turku, Finland. Markku.anttila@hormos-med.com
Sotaniemi
Eero A
EA
Pelkonen
Olavi
O
Rautio
Arja
A
D000368:Aged; D019540:Area Under Curve; D001711:Biotransformation; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007677:Kidney Function Tests; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D012642:Selegiline / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline