Pharmacokinetics of a new extended-release nifedipine formulation following a single oral dose, in human volunteers.
This study aimed to define the pharmacokinetics of nifedipine following oral administration of a new extended-release formulation. Twelve healthy volunteers of both sexes, aged 39 +/- 4 years, were treated with a single oral tablet of a new extended-release formulation containing 40 mg of nifedipine. Samples of venous blood were taken before dosing, after 30 min and at 1, 2, 4, 8, 12, 16, 20 and 24 h after administration. Nifedipine concentration was measured by means of a high-performance liquid chromatography method. Noncompartmental pharmacokinetics parameters were then calculated. The plasma concentration of nifedipine increased slowly and in seven subjects biphasic peaks occurred. The mean values were as follows: t(max): 8.5 +/- 1.2 h; C(max): 36.55 +/- 6.76 ng/ml; AUC: 347.06 +/- 51.61 ng/h/ml; AUC 409.99 +/- 61.08 ng/h/ml; A(half-life): 2.26 +/- 0.36 h; D(half-life): 2.43 +/- 0.44 h; E(half-life): 4.62 +/- 0.79 h. Twenty-four hours after administration nifedipine was still detectable (3.17 +/- 0.67 ng/ml). Arterial blood pressure decreased and heart rate increased concurrently and proportionally to the increase in nifedipine concentration. Extended-release nifedipine formulations have better tolerability profiles than immediate-release formulations, which are at present not recommended in the treatment of hypertension, hypertensive crises or myocardial infarction. This new extended-release formulation has interesting pharmacokinetic parameters and may be effective in conditions in which dihydropyridine calcium channel blockers are indicated.
Cainazzo
M M
MM
Clinical Pharmacology and Toxicology Section, University of Modena and Reggio Emilia, School of Medicine, Policlinico of Modena, Modena, Italy.
Pinetti
D
D
Savino
G
G
Bartiromo
M
M
Forgione
A
A
Bertolini
A
A
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D009543:Nifedipine