The effect of dosing regimen and food on the bioavailability of the extensively metabolized, highly variable drug Eldepryl® (selegiline hydrochloride)

American Journal of Therapeutics

Volumn 3, Issue 4, 1996, Pages 298-313

  Barrett, Jeffrey S ^a   Rohatagi, Shashank ^b   DeWitt, Kimberly E ^b   Morales, Richard J ^b   DiSanto, Anthony R ^b  

^a Somerset Pharmaceuticals   (United States)

^b NONE

Author keywords

highly variable drug; pharmacokinetics; Selegiline

Indexed keywords

AMPHETAMINE; DRUG METABOLITE; METHAMPHETAMINE; NORSELEGILINE; SELEGILINE; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; COMPARTMENT MODEL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG HALF LIFE; FOOD DRUG INTERACTION; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL;

EID: 0030008656     PISSN: 10752765     EISSN: None     Source Type: Journal    
DOI: 10.1097/00045391-199604000-00008     Document Type: Article

References (31)

1. Heinonen EH, Anttila MI, Lammintausta RAS: Pharmacokinetics and clinical pharmacology of selegiline. In: Inhibitors of Monoamine Oxidase B (Ed. Szelenyi I), Birkhauser Verlag Ag, Basel, 1992, pp. 201-213.
2. Reynolds GP, Riederer P, Sandler M, Jellinger K, Seemann D: Amphetamine and 2-phenylethylamine in postmortem parkinsonian brain after (-)deprenyl administration. J Neural Transm 1978;43:271-277.
3. Schacter M, Marsden CD, Parkes JD, Jenner P, Testa B: Deprenyl in the management of response fluctuations in patients with Parkinson's disease on levodopa. J Neurolog Neurosurg Psychiatry 1980;43:1016-1021.
4. Ellsworth JD, Sandier M, Lees AJ, Ward C, Stern GM: The contribution of amphetamine metabolites of (-)deprenyl to its antiparkinsonian properties. J Neural Transm 1982;54:105-110.
5. Karoum F, Chuang L-W, Eisler T, Calne DB, Liebowitz MR, Quitkin FM, Klein DF, Wyatt RJ: Metabolism of (-)deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: a biochemical assessment. Neurology 1982;32:503-509.
6. Liebowitz MR, Karoum F, Quitkin FM, Davies SO, Schwartz D, Levitt M, Linnoila M: Biochemical effects of 1-deprenyl in atypical depressives. Biol Psychiatry 1985; 20:558-565.
7. Roselaar SE, Langdon N, Lock CB, Jenner P, Parkes JD: Selegiline in narcolepsy. Sleep 1985;10(5):491-495.
8. Heinonen EH, Anttila M, Karnani H, Lammintausta R: Pharmacokinetics of selegiline after oral dosing. Mov Disord 1994;9(Suppl 1):P248.
9. Michaelis K, Waitzinger J, Agvaz U, Salama Z, Plettenberg H, Jaeger H: Pharmacokinetics of 1-deprenyl and n-desmethylselegiline in blood versus plasma after single dose oral administration of 10 mg selegiline. Pharm Res 1993;10:S331.
10. Heinonen EH: Selegiline in the treatment of Parkinson's disease: Pharmacokinetic and clinical studies. Academic Dissertation, University of Turku (Finland), 1995.
11. Mahmood I, Marinac JS, Willsie S, Mason WD: Pharmacokinetics and relative bioavailability of selegiline in healthy volunteers. Biopharm Drug Dispos 1995;16:535-545.
12. Yoshida T, Yamada Y, Yamamoto T, Kuroiwa Y: Metabolism of deprenyl, a selective monoamine oxidase (MAO) B inhibitor, in rat: Relationship of metabolism to MAO-B inhibitory potency. Xenobiotica 1986;16(2):129-136.
13. Yoshida T, Oguro T, Kuroiwa Y: Hepatic and extrahepatic metabolism of deprenyl, a selective monamine oxidase (MAO) B inhibitor, of amphetamines in rats: Sex and strain differences. Xenobiotica 1987;17(8):957-963.
14. Grace JM, Kinter MT, Macdonald TL: Atypical metabolism of deprenyl and its enantiomer, (S)-(+)-N,α-dimethyl-N-propynlphenethylamine, by cytochrome P450 2D6. Chem Res Toxicol 1994;7(3):286-290.
15. Knoll J, Magyar K: Some puzzling pharmacological effects of monoamine oxidase inhibitors. In: Monoamine Oxidases - New Vistas (Eds. Costa E, Sandier M), Raven Press, New York, 1972, pp. 393-408.
16. Mangoni A, Grassi MP, Frattola L, Piolti R, Bassi A, Motta A, Marcone A, Smirne S: Effects of a MAO-B inhibitor in the treatment of Alzheimer's disease. Eur Neurol 1991;31: 100-107.
17. The Parkinson Study Group: A controlled trial of lazabemide (R019-6327) in untreated Parkinson's disease. Ann Neurol 1993;33:350-356.
18. Berry MD, Juorio AV, Paterson LA: Possible mechanisms of action of (-)deprenyl and other MAO-B inhibitors in some neurologic and psychiatric disorders. Prog Neurobiology 1994;44:141-161.
19. Tatton WG: Selegiline can mediate neuronal rescue rather than neuronal protection. Movement Disorders 1993;8(Suppl 1):520-530.
20. Solo PT, Tatton WG: Deprenyl reduces the death of motoneurons caused by axotomy. J Neuroscience Res 1992;31:394-400.
21. Tatton WG, Ju WYL, Holland DP, Tai C, Kwan M: (-)-Deprenyl reduces PC 12 cell apoptosis by inducing new protein synthesis. J Neurochemistry 1994;63:1572-1575.
22. Waldmeier PC, Feiner AE: Deprenil: loss of selectivity for inhibition of B-type MAO after repeated treatment. Biochemical Pharmacol 1978;27:801-802.
23. The Parkinson Study Group: Effects of tocopheral and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 1993;328:176-183.
24. Tariot PN, Sunderland T, Weingartner H, Murphy DL, Welkowitz JA, Thompson K, Cohen RM: Cognitive effects of L-deprenyl in Alzheimer's disease. Psychopharmacology 1987;91:489-495.
25. Mann JJ, Aarons SF, Wilner PJ, Keilp JG, Sweeney JA, Pearlstein T, Frances AJ, Kolsis JH, Brown RP: A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl: a selective monoamine oxidase inhibitor. Arch Gen Psychiat 1989;46:45-50.
26. Perenyi A, Goswami U, Frecska E, Arató M, Bela A: L-Deprenyl in treating negative symptoms of schizophrenia. Psychiat Res 1992;42:189-191.
27. Oh C, Murray B, Bhattacharya N, Holland D, Tatton WG: (-)-Deprenyl alters the survival of adult murine facial motoneurons after oxotomy: increases in vulnerable C57BL strain but decreases in motor neuron degeneration mutants. J Neuroscience Res 1994;38:64-74.
28. Schulz R, Antonin K-H, Huffman E, Jedrychowski M, Nilsson E, Schick C, Bieck PR: Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline. Clin Pharmacol Ther 1989;46:528-536.
29. Welling P: Nutrient effects on drug metabolism and action in the elderly. Drug-Nutrient Interactions 1985;4: 173-207.
30. Lessard D, Beaudry F, Niggebrugge A: A new high-sensitivity HPLC/MS/MS method for the determination of selegiline and desmethylselegiline in human plasma. Pharm Res 1994;11(Suppl 10):S-17.
31. Lam FC, Hung CT, Perrier DG: Estimation of variance for harmonic mean half-lives. J Pharm Sci 1985;74(2):229-231.