Persistence of antihypertensive efficacy after missed doses: comparison of amlodipine and nifedipine gastrointestinal therapeutic system.
OBJECTIVE
In this randomized, double-blind, crossover study, the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) was compared following missed doses. Design and methods In a randomized crossover design, 42 patients were randomized to receive amlodipine (5-10 mg) or the GITS formulation of nifedipine (nifedipine GITS) (30-60 mg) once daily for 12 weeks, then vice versa. During weeks 8, 10 and 12 of each treatment period, compliance failures were simulated by patients missing 0, 1 or 2 doses of their medication, and ambulatory systolic (SBP) and diastolic (DBP) blood pressure measurements were obtained.


RESULTS
Following steady-state treatment (i.e. 'perfect compliance'), there was no difference between amlodipine and nifedipine GITS in SBP (140.1 versus 134.2 mmHg) or DBP (84.0 versus 85.8 mmHg) at 0-24 h post-dose. When compliance was not perfect, i.e. when one or two doses were missed, DBP was maintained at a significantly lower level with amlodipine compared with nifedipine GITS at 24-48 h post-dose (83.1 versus 86.4 mmHg, P = 0.005) and at 48-72 h post-dose (84.2 versus 89.7 mmHg, P < 0.001). Plasma concentrations of amlodipine were better maintained than those of nifedipine GITS. At 72 h post-dose, the plasma concentration of amlodipine was 61% (17.0 +/- 11.2 ng/ml) compared with < 25% (28.3 +/- 49.9 ng/ml) for nifedipine GITS.


CONCLUSIONS
During short periods of non-compliance, antihypertensive efficacy remains more predictable with amlodipine than with nifedipine GITS.
Elliott
Henry L
HL
Western Infirmary, Glasgow, UK. HLE1B@clinmed.gla.ac.uk
Elawad
Mamoun
M
Wilkinson
Robert
R
Singh
Shyam P
SP
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000097:blood / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000097:blood / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D018592:Cross-Over Studies; D004064:Digestive System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000097:blood / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D017311:Amlodipine; D009543:Nifedipine