Effects of dosage and CYP2D6-mutated allele on plasma concentration of paroxetine - PubMed (original) (raw)

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

Kazushi Sawamura et al. Eur J Clin Pharmacol. 2004 Oct.

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.

PubMed Disclaimer

References

    1. Lancet. 1990 Sep 1;336(8714):529-32 - PubMed
    1. Mol Pharmacol. 1989 Jul;36(1):89-96 - PubMed
    1. Neuropsychopharmacology. 2003 Aug;28(8):1501-5 - PubMed
    1. Acta Psychiatr Scand Suppl. 1989;350:60-75 - PubMed
    1. Pharmacogenetics. 1995 Aug;5(4):215-23 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources