The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population.
OBJECTIVE
To determine the frequency of CYP2D6 poor metabolizers (PMs) in a Faroese patient group medicated with amitriptyline (AT) and to investigate plasma concentrations of AT and metabolites in relation to CYP2D6.


METHODS
CYP2D6 phenotype and genotype were determined in 23 Faroese patients treated with AT. Plasma concentrations of AT and metabolites were determined by high-performance liquid chromatography and investigated in relation to CYP2D6 activity.


RESULTS
Of the 23 patients phenotyped and genotyped, five (22%) (95% confidence interval 7.5, 43.7) were CYP2D6 PMs. No difference was found in AT daily dosage between PMs (median 25 mg day(-1); range 5-80) and extensive metabolizers (EMs) (median 27.5 mg day(-1); range 10-100). The (E)-10-OH-nortriptyline (NT)/dose concentrations were higher in EMs than in PMs and the NT/(E)-10-OH-NT and AT/(E)-10-OH-AT ratios were higher in PMs compared with EMs. The log sparteine metabolic ratio correlated positively with the NT/(E)-10-OH-NT ratio (r(s) = 0.821; P < 0.0005) and the AT/(E)-10-OH-AT ratio (r(s) = 0.605; P < 0.006).


CONCLUSIONS
A high proportion of CYP2D6 PMs was found in a Faroese patient group medicated with AT. However, similar doses of AT and concentrations of AT and NT were noted in EMs and PMs, probably due to varying doses and indications for AT treatment.
Halling
Jónrit
J
Institute of Public Health, Clinical Pharmacology, University of Southern Denmark, Odense, Denmark. jhalling@health.sdu.dk
Weihe
Pál
P
Brosen
Kim
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000639:Amitriptyline / Q000378:metabolism*; D000929:Antidepressive Agents, Tricyclic / Q000378:metabolism*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000378:metabolism*; D011110:Polymorphism, Genetic
D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D009661:Nortriptyline; D019389:Cytochrome P-450 CYP2D6