Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects.
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Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects. / Wuttke, Henrike; Rau, Thomas; Roland, Heide; Bergmann, Klaus; Böhm, Michael; Weil, Joachim; Werner, Dierk; Eschenhagen, Thomas.
In: CLIN PHARMACOL THER, Vol. 72, No. 4, 4, 2002, p. 429-437.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects.
AU - Wuttke, Henrike
AU - Rau, Thomas
AU - Roland, Heide
AU - Bergmann, Klaus
AU - Böhm, Michael
AU - Weil, Joachim
AU - Werner, Dierk
AU - Eschenhagen, Thomas
PY - 2002
Y1 - 2002
N2 - OBJECTIVE: The CYP2D6 genotype is a major determinant of interindividual differences in metoprolol plasma clearance. Cytochrome P450 2D6 (CYP2D6) poor metabolizers exhibit 3- to 10-fold higher plasma concentrations after administration of metoprolol than extensive metabolizers. However, the impact of the CYP2D6 genotype on the occurrence of adverse effects of metoprolol remains controversial. This study addressed whether the incidence of poor metabolizers was higher in patients with metoprolol-associated adverse effects than in the German population at large. METHODS: Approximately 1200 German physicians were asked to report on patients who had experienced pronounced adverse effects in association with administration of metoprolol. CYP2D6 genotypes were determined with a combination of allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. The adverse effects, consisting of symptoms related to beta-adrenergic receptor blockade and nonspecific symptoms, were recorded by use of a standardized questionnaire. RESULTS: Twenty-four patients were included in the study. Nine patients had 2 null alleles (poor metabolizer genotype; 38%); the remaining 15 had either 1 null allele (n = 7) or no null alleles (n = 8). Therefore the occurrences of poor metabolizer genotypes in the study population were 4.9- and 5.2-fold more frequent, respectively, than that found in unselected members of the German population in two large studies (P
AB - OBJECTIVE: The CYP2D6 genotype is a major determinant of interindividual differences in metoprolol plasma clearance. Cytochrome P450 2D6 (CYP2D6) poor metabolizers exhibit 3- to 10-fold higher plasma concentrations after administration of metoprolol than extensive metabolizers. However, the impact of the CYP2D6 genotype on the occurrence of adverse effects of metoprolol remains controversial. This study addressed whether the incidence of poor metabolizers was higher in patients with metoprolol-associated adverse effects than in the German population at large. METHODS: Approximately 1200 German physicians were asked to report on patients who had experienced pronounced adverse effects in association with administration of metoprolol. CYP2D6 genotypes were determined with a combination of allele-specific polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. The adverse effects, consisting of symptoms related to beta-adrenergic receptor blockade and nonspecific symptoms, were recorded by use of a standardized questionnaire. RESULTS: Twenty-four patients were included in the study. Nine patients had 2 null alleles (poor metabolizer genotype; 38%); the remaining 15 had either 1 null allele (n = 7) or no null alleles (n = 8). Therefore the occurrences of poor metabolizer genotypes in the study population were 4.9- and 5.2-fold more frequent, respectively, than that found in unselected members of the German population in two large studies (P
M3 - SCORING: Zeitschriftenaufsatz
VL - 72
SP - 429
EP - 437
JO - CLIN PHARMACOL THER
JF - CLIN PHARMACOL THER
SN - 0009-9236
IS - 4
M1 - 4
ER -