Comparative pharmacokinetics of two nifedipine products in capsule form following single oral administration in healthy volunteers

Abstract

The pharmacokinetic parameters (AUC, Cmax, Tmax, and t1/2) of nifedipine following single oral administration of a 10 mg capsule of test product were compared to those of the same amount of a reference product. The two products in capsule form were administered according to a randomized two-way crossover design in 22 healthy male volunteers. Nifedipine plasma concentrations were determined using a rapid, sensitive and precise high performance liquid chromatography (HPLC) method with ultraviolet (UV) detection at 235 nm. The parametric 90% confidence intervals of the mean value of the ratio [Myogard (test product) /Adalat (reference product)] for pharmacokinetic parameters were 0.90-1.08, 0.80-1.07, and 0.93-1.12 for AUC0-->infinity, Cmax and t1/2, respectively. In each case, values were within the acceptable bioequivalence range of 0.8-1.25. Distribution free point estimate for the difference in expected medians of Tmax of the two products (Myogard-Adalat) was 0.00 h with a 90% confidence interval of 0.00-0.13 which is greater than the accepted bioequivalence of +/- 0.12. The kinetic parameters were comparable to those reported for nifedipine, and no statistically significant differences were found in any of them when comparing the two products by analysis of variance (ANOVA) on log-transformed data. Thus, the two products could be considered bioequivalent regarding absorption rate (Cmax and Tmax), extent of absorption (Cmax and AUC) and elimination (t1/2).

The Effect of Silymarin on Oral Nifedipine Pharmacokinetics

“…Mean pharmacokinetic parameters for both nifedipine and free silibinin observed in the present study are similar to those reported in the literature [9], [26], [27], [28], [29]. Specifically, silibinin exposure with C max values of up to 0.4 mM was in the expected range [9].…”

“…In contrast, intraindividual variability of nifedipine pharmacokinetics was higher than reported. Multiplicative coefficients of variation below 17 % and 30 % for the AUC and Cmax, respectively, were expected [26], [27]. The intraindividual CV found here for AUC was 25 %, that for C max reached 120 %.…”

“…There was, however, no significant correlation between silibinin exposure and TEST/REFER-ENCE ratios (data not shown). Because there is no obvious reason why intraindividual variability for administration of nifedipine alone should be remarkably higher than values reported for immediate release nifedipine in literature [26], [27], we cannot exclude that silymarin administration may have contributed to the apparent high intraindividual variability. given 10 hours and 90 minutes, respectively, prior to nifedipine administration).…”

CPU0213, A NON‐SELECTIVE ETA/ETB RECEPTOR ANTAGONIST, IMPROVES PULMONARY ARTERIOLAR REMODELING OF MONOCROTALINE‐INDUCED PULMONARY HYPERTENSION IN RATS

“…Thus, the severity of the pathology of the PH between the two studies is different. Second, amlodipine has a longer half‐life 28,29 than nifedipine 30 (3.08 ± 1.61 vs 0.93–01.12 h, respectively). Both these factors may contribute to the differences in the effects between nifedipine and amlodipine in attenuating PH 28 …”

Desirability function approach for the optimization of an in-syringe ultrasound-assisted emulsification-microextraction method for the simultaneous determination of amlodipine and nifedipine in plasma samples

“…There have been numerous publications describing the determination of nifedipine concentrations in plasma or serum such as HPLC–UV and electrochemical detection , SPE on cyano cartridges with HPLC–UV , and GC–MS . Also, different methods for the quantification of AMB have been reported which include TLC , GC with various detection methods and HPLC–UV , LC–MS/MS , and fluorimetry detection .…”