Background: Antihypertensive therapy aims to reduce long-term morbidity and mortality. Drugs characterized by controlled release show a better pharmacokinetic and pharmacodynamic profile compared to standard formulations.
Methods: The present study evaluated the effects of nifedipine controlled release (0.33, 0.66 and 1.32 mg/kg per os), nifedipine standard (0.08, 0.165 and 0.33 mg/kg per os) and amlodipine (0.08, 0.165 and 0.33 mg/kg per os) on mean arterial blood pressure, heart rate and pressure rate index of spontaneously hypertensive rats (SHR). These were treated by gastric gavage, and analyzed after 30 min, 1, 3, 6, 12, and 24 hours. Moreover, plasma levels of nifedipine and amlodipine were also assayed by high-performance liquid chromatography.
Results: Nifedipine controlled release showed a longer antihypertensive effect when compared with standard formulation and with amlodipine. The highest dose of nifedipine controlled release decreased blood pressure soon after 1 hour with a maximum decrease (-20 mmHg) at 3 hours. The effect was still significant 24 hours later (p < 0.05). Amlodipine antihypertensive effect lasted 12 hours with a maximum decrease of 18 mmHg at 6 hours. The treatment of SHR rats with nifedipine controlled release, at each of the tested doses, did not cause any significant alterations in heart rate recorded at the beginning of the experiments. Nifedipine standard (0.165 and 0.33 mg/kg) and amlodipine (0.33 mg/kg) increased heart rate in SHR rats. Interestingly enough, pressure rate index was slightly affected by nifedipine standard release and amlodipine whereas it was remarkably reduced by nifedipine controlled release (p < 0.01 vs vehicle until 9 hours). All the compounds showed maximum plasma concentrations paralleled by maximum antihypertensive effects, as evidenced at high-performance liquid chromatography method.
Conclusions: Nifedipine controlled release showed more pronounced antihypertensive effects and longer pharmacokinetic properties with respect to nifedipine standard release and amlodipine.