Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans

British Journal of Clinical Pharmacology
Y BöttigerL Bertilsson

Abstract

1. Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia. 2. Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-alpha-methoxy-9,10-dihydrolysergol (MMDL), which is further N-demethylated to form 10-alpha-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms. 3. After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes. 4. The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l-1 and AUC (0, th) 144 nmol l-1h, mean MDL Cmax 183 nmol l-1 and AUC 2627 nmol l-1h) but were markedly different from the five subjects who were poor metabolise...Continue Reading

Citations

Aug 1, 2008·Clinical Drug Investigation·Bengt WinbladAlina Solomon
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Oct 13, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Nov 12, 2009·Clinical Pharmacokinetics·Shu-Feng Zhou
Sep 23, 2014·BioMed Research International·Bernd SaletuAhsan Shoeb
Jun 9, 2006·Medicina clínica·Hortensia Alonso-NavarroJosé A García-Agúndez

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Genetics

Alzheimer's disease is a neurodegenerative disease. Discover genetic and epigenetic aspects of Alzheimer’s disease, including genetic markers and genomic structural variations with this feed.