Key Points
- To evaluate the relationship between metoprolol metabolic ratio, CYP2D6*10B genotype, and paroxetine disposition in Korean subjects.
- Oral administration of a single 40-mg dose of paroxetine to one poor metabolizer and 15 healthy subjects.
- Use of metoprolol metabolic ratio to categorize extensive metabolizers among 223 Korean participants.
- Determination of genotypes using allele-specific polymerase chain reaction and GeneChip microarray.
- Nonlinear relationship observed between the oral clearance and AUC of paroxetine and metoprolol MR (correlation coefficients of 0.82 and 0.91, respectively, P < 0.05).
- Extensive metabolizers homozygous or heterozygous for CYP2D6*10B had lower oral clearance values of paroxetine compared to those homozygous for CYP2D6*1/*1.
- Subjects homozygous for CYP2D6*10B exhibited a significantly higher AUC of paroxetine (666.4 +/- 169.4 ng/mL x h) than those homozygous for the wild type (194.5 +/- 55.9 ng/mL x h).
Structured PICO
Does CYP2D6*10 genotype and metoprolol metabolic ratio predict paroxetine disposition in Korean subjects?
PPopulation16 Korean subjects (1 poor metabolizer and 15 healthy extensive metabolizers whose phenotypes were predetermined by metoprolol metabolic ratio)
IInterventionSingle 40-mg oral dose of paroxetine
OOutcomePharmacokinetic parameters (oral clearance and area under the plasma concentration versus time curve [AUC]) of paroxetinesurrogate
CYP2D6 activity measured by metoprolol metabolic ratio is a strong predictor of paroxetine disposition in Korean extensive metabolizers, though genotype alone is not a perfect predictor.