Impact of the CYP2D6 genotype on the clinical effects of metoprolol: a prospective longitudinal study.
After administration of metoprolol, plasma concentrations of the drug are markedly higher in CYP2D6 poor metabolizers (PMs) than in non-PMs. In a prospective double-blind 3-month study, we investigated whether this translates into differences in metoprolol's effects after initiation of therapy. Despite administering equal doses to PMs and non-PMs, metoprolol plasma concentrations were 4.9-fold higher in the PM group. Metoprolol evoked significantly and persistently greater reductions in heart rate, diastolic blood pressure, and mean arterial pressure in PMs than in non-PMs. It appears, therefore, that the CYP2D6 genotype contributes to interindividual differences in metoprolol response.
Rau
T
T
Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. t.rau@uke.uni-hamburg.de
Wuttke
H
H
Michels
L M
LM
Werner
U
U
Bergmann
K
K
Kreft
M
M
Fromm
M F
MF
Eschenhagen
T
T
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000187:drug effects; D011446:Prospective Studies
D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol