A099: Clinical efficacy of nebivolol in hypertensive patients based on cytochrome p-450 2d6 phenotype

Objectives: To evaluate the efficacy of Nebivolol (N), a beta-blocking agent, in hypertensive patients classified as extensive metabolizers (EM) or non-extensive metabolizers (non-EM) based on phenotype for cytochrome 2D6. Methods: Approximately 400 hypertensive patients (clinic DBP ≥ 95 mm Hg) were...

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Bibliographic Details
Published in:American journal of hypertension 2000-04, Vol.13 (S2), p.148A-148A
Main Authors: Poirier, L., Lefebvre, J., Lacourcière, Y.
Format: Article
Language:English
Subjects:
beta-blockers
cytochrome P450
Hypertension
nebivolol
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Summary:Objectives: To evaluate the efficacy of Nebivolol (N), a beta-blocking agent, in hypertensive patients classified as extensive metabolizers (EM) or non-extensive metabolizers (non-EM) based on phenotype for cytochrome 2D6. Methods: Approximately 400 hypertensive patients (clinic DBP ≥ 95 mm Hg) were phenotyped for P-450 2D6 polymorphism. Each screened patient was instructed to take dextrometorphan 30 mg at bedtime and to collect urine overnight. Based on metabolic ratio (MR) (dextrometorphan/dextrorphan), patients were classified as EM (MR < 0.30) or non-EM (MR > 0.30). A total of 37 patients (18 EM and 19 non-EM) were enrolled in the study and matched for age and sex. After a 2–4 week placebo period, patients received N 5 mg o.d. for 12 weeks. Clinic sitting BP was measured at baseline and after 12 weeks of treatment at trough and at peak, 2 hours after drug intake. Results: N induced significant (p < 0.0001) and non-statistically different systolic/diastolic BP decrements at trough after 12 weeks of treatment in the EM group (−9.0/−10.3 mm Hg) and in the non-EM group (−12.3/−9.5 mm Hg). Heart rate was significantly (p < 0.0001) and similarly decreased in both EM and non-EM (−8.7; −6.6 beats/min, respectively) treatment groups. BP measured at peak revealed that N induced additional trough to peak systolic/diastolic BP decrements in the EM group (−5.2/−4.6 mm Hg) and in the non-EM group (−11.4/−7.9 mm Hg). However, non-significant additional heart rate decreases were produced by N at peak in both EM and non-EM groups (−4.2; −3.3 beats/min, respectively). Treatment with N was well tolerated in both EM and non-EM groups with a similar incidence of side effects. Conclusion: N induced significant and similar reductions in clinic BP and heart rate in both groups. Our results do not support the hypothesis that patients identified as non-EM and treated with N will experience more pronounced antihypertensive effects and a different tolerability profile than EM patients.
ISSN:0895-7061
1879-1905
1941-7225
DOI:10.1016/S0895-7061(00)00632-4