Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans

British Journal of Clinical Pharmacology

Volumn 42, Issue 6, 1996, Pages 707-711

  Bottiger Y ^a   Dostert, P ^b   Strolin Benedetti, M ^c   Bani, M ^b   Fiorentini, F ^b   Casati, M ^b   Poggesti, I ^b   Alm, C ^a   Alvan, G ^a   Bertilsson, L ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^b PFIZER INC   (United States)

^c Zambon Group SpA   (Italy)

Author keywords

CYP2D6; debrisoquine; nicergoline

Indexed keywords

DEBRISOQUINE; DRUG METABOLITE; MEPHENYTOIN; NICERGOLINE;

ADULT; AREA UNDER THE CURVE; ARTICLE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG HYDROLYSIS; DRUG METABOLISM; DRUG STRUCTURE; ENZYME ACTIVITY; FEMALE; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; PHENOTYPE; PRIORITY JOURNAL;

EID: 10544231870     PISSN: 03065251     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2125.1996.00471.x     Document Type: Article

References (13)

1. Arrigo A, Moglia A, Borsotti, L, et al. A double-blind, placebo-controlled cross-over trial with nicergoline in patients with senile dementia. Int J Pharm Res 1982; 2 (Suppl.1): 33-41.
2. Nicergoline Cooperative Group. A double-blind randomised study of two ergot-derivatives in mild to moderate dementia. Curr Ther Res 1990; 48: 597-612.
3. Battaglia A, Bruno G, Ardia A, Sacchetti G. Nicergoline in mild to moderate dementia: A multicenter, double-blind placebo controlled study. J Am Geriatric Soc 1989; 37: 295-302.
4. Bellotti V, Jannuzzo MG, Moro E, Jori C, Dubini A, Strolin Benedetti M. Plasma pharmacokinetics of nicergoline metabolites in healthy volunteers. Eur J Clin Pharmacol 1989; 36 (Suppl.): A150.
5. Johnston A, Abrams SM, Patel M, et al. Bioequivalence of controlled release nicergoline 60 mg once daily vs the plain form 30 mg twice daily in 24 male subjects. Br J Clin Pharmacol 1993; 35: 80P.
6. Poggesi I, Strolin Benedetti M, Berti CA, Dubini A, Pelluzzoni C, Dostert P. Does nicergoline N-demethylation follow a bimodal distribution? J Basic Clin Physiol Pharmacol 1992; 3 (Suppl.): 255.
7. Alvan G, Bechtel P, Iselius L, Gundert-Remy U. Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol 1990; 39: 533-537.
8. Bertilsson L, Lou Y-Q, Du Y-L, et al. Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquine and S-mephenytoin. Clin Pharmacol Ther 1992; 51: 388-397.
9. Alvan G, Graffner C, Gustavsson LL, et al. Tolerance and pilot pharmacokinetics of amiflamine after increasing single oral doses in healthy subjects. Clin Pharmacol Ther 1986; 40: 81-85.
10. Foresti E, Sabatino P, Riva di Sanseverino L, Fusca R, Tosi C, Tonani R. Structure and molecular orbital study of ergoline derivatives. 1-(6-Methyl-8 beta-ergolinylmethyl) imidazolidine-2,4-dione (I) and 2-(10-methoxy-1,6-dimethyl-8 beta-ergolinyl)ethyl 3,5-dimethyl-1H-2-pyrrole-carboxylate toluene hemisolvate (II) and comparison with nicergoline (III). Acta Crystallogr B 1988; 44: 307-315.
11. Meyer UA, Gut T, Kronbach T, et al. The molecular mechanisms of two common polymorphisms of drug oxidation - evidence for functional changes in cytochrome P-450 isozymes catalysing bufuralol and mephenytoin oxidation. Xenobiotica 1986; 16: 449-464.
12. Koymans L, Vermeulen NP, van Acker SA, et al. A predictive model for substrates of cytochrome P450-debrisoquine (2D6). Chem Res Toxicol 1992; 5: 211-219.
13. Dayer P. Advantages and drawbacks of probe drugs for the assessment of phenotypic expression of cytochrome P-450 db1 (P450 IID6). In European Consensus Conference on Pharmacogenetics, eds Alvan G, Balant LP, Bechtel PR, Boobis AR, Gram LF, Pithan K, Commission of the European Communities, Luxembourg, 1990: 33.