Pharmacokinetic and Tolerability Comparison of Sustained and Immediate Release Oral Formulations of Nifedipine Tablet Formulations: A Single-Dose, Randomized, Open-Label, Two-Period, Two-Way Crossover Study in Healthy, Fasting Egyptian Male Volunteers.

Abstract

Nifedipine is one of calcium channel blockers that commonly used clinically to treat hypertension and angina in Egyptian patients. A sustained-release (SR) formulation of nifedipine is available in the Egyptian community and administered twice daily. This study aimed to to compare the pharmacokinetics and safety profiles of a 20 mg SR and IR (immediate release) formulation of nifedipine after single-dose administration in healthy Egyptian subjects. Randomized, crossed open-label two- way clinical trial, in 16 healthy adult volunteers, of 24.75±5.20 years, with BMI 23.26±1.756 were assessed. Blood samples were collected at predefined times for 48 h and analyzed for Nifedipine plasma concentrations using validated reversed phase liquid chromatography method with ultraviolet detection. Pharmacokinetics was determined using non- compartmental model pharmacokinetics and analyzed using one-way ANOVA (P≤0.05). Following a single oral administration, SR formulation had a lower Cmax, compared to IR formulation (54.46±17.75 , 107.45±29.85 ng/mL, respectively), and Tmax was significantly longer (2.97 vs. 1.13 h) for the SR and IR formulation, respectively. There was no significant difference between the SR and the IR formulations for AUC0-last and AUC0-∞ (326.7±98.28 vs. 309.27±105.53 ng·h·mL-1 and 380.9 ± 105.24 vs. 334.36±108.1 ng·h·mL-1, respectively). SR formulation of nifedipine showed similar pharmacokinetics to the IR Formulation (F%=1.049), but it additionally allows a less frequent administration. Therefore, The nifedipine SR and IR formulations were well tolerated and displayed comparable safety profiles.