Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine.
A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.
Wagner
F
F
Benedikt Kreutz Rehabilitationszentrum für Herz- und Kreislaufkranke, Bad Krozingen.
Jähnchen
E
E
Trenk
D
D
Eichelbaum
M
M
Harnasch
P
P
Hauf
G
G
Roskamm
H
H
D000787:Angina Pectoris / Q000188:drug therapy*; D004110:Diltiazem / Q000009:adverse effects* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006327:Heart Block / Q000139:chemically induced; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008657:Metabolic Clearance Rate; D008790:Metoprolol / Q000009:adverse effects* / Q000493:pharmacokinetics; D008875:Middle Aged; D010641:Phenotype; D011405:Propafenone / Q000009:adverse effects* / Q000493:pharmacokinetics; D013034:Sparteine / Q000009:adverse effects* / Q000493:pharmacokinetics
D013034:Sparteine; D011405:Propafenone; D004110:Diltiazem; D008790:Metoprolol