Format

Send to

Choose Destination
Eur J Clin Pharmacol. 2004 Oct;60(8):553-7. Epub 2004 Sep 3.

Effects of dosage and CYP2D6-mutated allele on plasma concentration of paroxetine.

Author information

1
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahimachidori-ichibancho, 951-8510 Niigata, Japan.

Abstract

OBJECTIVE:

We investigated the effect of dosages of paroxetine and cytochrome P450 (CYP) 2D6 genotypes on the plasma concentration of paroxetine in Japanese patients being treated with paroxetine.

METHODS:

Blood samples were collected from 73 individuals after at least 2 weeks of the same daily dose of paroxetine. The plasma paroxetine concentration was measured using HPLC, and the CYP2D6 genotypes were identified by PCR. Genotype groups were compared by one-way analysis of variance at different paroxetine doses.

RESULTS:

The mean plasma paroxetine concentrations at daily doses of 10, 20, 30, and 40 ng/ml were 6.6+/-7.4, 34.9+/-26.8, 74.8+/-37.2, and 130.5+/-96.8 ng/ml, respectively, showing a disproportionate and nonlinear increase in plasma drug levels of paroxetine upon increasing doses. Plasma paroxetine concentrations in patients with CYP2D6*10 alleles were significantly higher than those without *10 allele at 10 mg/day (7.3+/-6.11 vs. 2.99+/-3.52 ng/ml), but there was no significant difference between *1/ *1, *1/ *10 and *10/ *10 genotypes at the higher doses. Similarly, patients with CYP2D6*5 alleles showed higher plasma paroxetine concentrations than those without *5 allele, although differences in the plasma paroxetine concentration did not reach statistical significance level because of the small number of subjects with *5 alleles.

CONCLUSIONS:

Our results indicate the possibility of saturation in paroxetine metabolism with an increase in paroxetine dose, and that CYP2D6*10 allele(s) have significant impact on plasma paroxetine concentration at low doses in Japanese population.

PMID:
15349705
DOI:
10.1007/s00228-004-0792-6
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center