Requirements for drug monitoring of verapamil: experience from an unselected group of patients with cardiovascular disease.
Serum verapamil and metabolite concentrations were determined by HPLC in 29 patients in routine treatment with verapamil, and 23 were in steady state. Dosage levels and corresponding mean trough levels (+/- S.D.) were as follows: 120 mg daily: 79.1 (+/- 77) nmol/l, 240 mg daily: 173.3 (+/- 200.1) nmol/l, 360 mg daily: 204 (+/- 110.2) nmol/l and 480 mg daily: 361.0 (+/- 231.4) nmol/l. The variation coefficients were 97.3, 115.4, 54.0, and 62.1, respectively, thus showing considerable interpatient variation. Repeated determination of trough levels showed, in contrast, only small intrapatient variation (variation coefficient 35.8, 1.9, and 7.4, at the dosage levels 120, 240 and 340 mg per day). No significant correlation was found between serum verapamil levels age, sex, or weight. No significant effect of digoxin on the concentration of serum verapamil was found. No relation was observed between serum verapamil concentrations and desired effect or side-effects. Two patients showed no measurable serum verapamil, but one of these had detectable levels of metabolites. Such patients may represent subgroups of fast metabolizers or non-absorbers. Measurements of the metabolites nor-verapamil, D 620 and D 617 indicated saturation of the first-pass metabolism. In conclusion, therapeutic drug monitoring is not indicated during routine verapamil treatment, whereas single measurements of verapamil may be warranted in patients not responding to treatment in order to identify fast metabolizers or non-absorbers.
Husum
D
D
Department of Cardiology, University of Copenhagen, Hvidovre Hospital, Denmark.
Johnsen
A
A
Jensen
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001711:Biotransformation; D002318:Cardiovascular Diseases / Q000097:blood* / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009570:Nitriles; D012044:Regression Analysis; D014700:Verapamil / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use
D009570:Nitriles; C016906:alpha-(3-aminopropyl)-3,4-dimethoxy-alpha-(1-methylethyl)benzeneacetonitrile; C482241:2-(3,4-dimethoxyphenyl)-5-amino-2-isopropylvaleronitrile; C016904:norverapamil; D014700:Verapamil