Author: Najia Rahim, Syed Baqir Shyum Naqvi, Mehtab Alam, Abdur Rasheed and Urooj Abdul Khalique
Publishing Date: 2016
E-ISSN: 1011-601X
Volume: 29 Issue: 2
ABSTRACT:
The current study was aimed to judge bioequivalence between two formulations of cefadroxil capsules as guided by FDA guidelines. Another objective was to conduct pharmacokinetic evaluation in Pakistani population. A single-dose, randomized, cross-over pharmacokinetic study was conducted during the month of May’2013 to August’2013. Washout period was one week. Fourteen healthy male adult volunteers were enrolled in the study, however twelve completed the study. Cefadroxil plasma concentration was analyzed by using validated HPLC method. Protein precipitation was achieved by the addition of 6% tri chloro acetic acid in 1:1 ratio and detection was done at 260 nm. Retention time was 7.792 min and correlation coefficient (R2) was 0.9953 showing linearity of the method. Blood sampling was carried out at different time intervals after administration of either test (TEST 500 mg) or reference (REF® 500mg) formulation. Pharmacokinetic parameters (AUC0→∞, AUC0→t, Cmax, Tmax, t1/2 and kel) were calculated using Kinetica® PK/PD software. The geometric mean ratios and 90% confidence interval (CI) of these pharmacokinetic parameters for cefadroxil (test and reference) formulations were 0.986 (90.83-106.98%) for AUC0-t; 0.967 (89.13- 104.92%) for AUC0-∞ and 0.999 (91.06-109.69%) for Cmax. The differences between Tmax of both formulations were not found to be statistically significant (p-value was more than 0.05). The 90% CI of the test/reference AUC and Cmax ratio of cefadroxil were within the FDA recommended range for bioequivalence. Maximum plasma concentration Cmax was 12.5 μg/ml for test and 12.47μg/ml for reference formulations. Average time to reach Cmax for test and reference formulation was 1.54 and 1.5 hrs. The two formulations of cefadroxil studied during the above study were verified bioequivalent. Maximum plasma concentration of cefadroxil was lower than those mentioned in some previous studies, while Tmax and half-life were near to values reported in literature
KEYWORDS: FDA; cefadroxil; pharmacokinetic study; comparative bioavailability.