Bioequivalence study of two formulations of candesartan cilexetil tablet in healthy subjects under fasting conditions

Abstract

IntroductionThe present study was conducted to compare the bioavailability of two candesartan cilexetil 16 mg tablet formulations (test and reference formulations).Materials and methodsThis study was a randomized, single- blind, two-period, cross-over study which included 24 healthy adult male and female subjects under fasting conditions. The pharmacokinetic parameters were determined based on the concentrations of candesartan (CAS 139481-59-7), using ultra-pressure high-performance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout period of 1 week), a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration time curve (AUC) from time 0 hours to 24 hours, AUC from time zero to infinity, the peak plasma concentration of the drug (Cmax), time to achieve the Cmax, and the elimination half-life.ResultsThe geometric mean ratios (90% confidence interval) of the test drug/reference drug for candesartan were 100.92% (92.15%–110.52%) for the AUC from 0 hours to 24 hours, 100.24% (92.24%–108.95%) for the AUC from time zero to infinity, and 106.71% (93.20%–122.18%) for the Cmax. The differences between the test and reference product in the time to achieve Cmax values and elimination half-life values were not statistically significant (P > 0.05). The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of candesartan were within the acceptance range for bioequivalence. There was no adverse event encountered during this bioequivalence study.ConclusionIt was concluded that the two candesartan tablet formulations (the test and reference product) were bioequivalent.

Pharmacodynamics Effect of Methylprednisolone Tablets on the Serum Concentration of Annexin A1: In Vivo Comparative Study Between Generic and Innovator Drug

“…Similar results were also obtained by Cooper-Dehoff and Elliott who compared patent and generic drugs of some blood pressure lowering agents that included beta-blockers, diuretics, and calcium antagonists [10]. Some other studies on clopidogrel and candesartan tablets also reported bioequivalence between their patent and generic products [11,12].…”

Pharmacokinetic and Bioequivalence Studies of a Newly Developed Branded Generic of Candesartan Cilexetil Tablets in Healthy Volunteers

“…The intrasubject CV of C max, AUC 0–t , and AUC 0–∞ for the pilot study (13.5%–15.0%) was lower than those in the pivotal study (22.8%–24.4%); however, they were within the range for similar (14.7%–33%) reported for healthy volunteer studies for candesartan . In conclusion, the 16‐mg candesartan cilexetil test formulation 2 was found to be bioequivalent to the innovator following a single‐dose crossover study in healthy fasted subjects.…”

“…in the pivotal study (22.8%-24.4%); however, they were within the range for similar (14.7%-33%) reported for healthy volunteer studies for candesartan. [10][11][12][13] In conclusion, the 16-mg candesartan cilexetil test formulation 2 was found to be bioequivalent to the innovator following a single-dose crossover study in healthy fasted subjects. The study met the ANMAT regulatory criteria for bioequivalence in healthy subjects.…”

A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole

“…With this concept, drug regulators require that generic formulations should have equivalent clinical effects with its innovator counterparts, resulting in interchangeability of both products. In compliance with the requirement, we have also conducted bioequivalence studies on several generic formulations [21,22,23,24]. Our current study on pramipexole was carried out with the same requirements in mind.…”