The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population

AIM
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 (rs = 0.821; P < 0.0005) and the AT/(E)-10-OH-AT
ratio (rs = 0.605; P < 0.006).

CONCLUSION
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.