Bioequivalence Study of Two Azithromycin Formulations in Healthy Subjects

Abstract

The study was conducted to find out whether the bioavailability of a 500 mg azithromycin (CAS 83905-01-5) tablet (Zycin, test) was equivalent to that of a reference formulation. The pharmacokinetic parameters assessed in this study were the area under the plasma concentration-time curve from time zero to 120 h (AUCt), area under the plasma concentration-time curve from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve the peak plasma concentration (tmax), and the elimination half-life (t1/2). This was a randomized, single blind, two-period, cross-over study which included 18 healthy adult male and female subjects under fasting conditions. In each of the two study periods (separated by a washout of two weeks) a single dose of test or reference drug was administered. Blood samples were taken up to 120 h post dose, the plasma was separated and the concentrations of azithromycin were determined by a LC-MS/MS method. In this study, the mean AUCt, AUCinf, Cmax, and t1/2 of azithromycin from the test drug were 4967.49 ng x h x mL(-1), 5871.74 ng x h x mL(-1), 412.14 ng/mL, and 51.32 h, respectively. The mean AUCt, AUCinf, Cmax, and t1/2 of azithromycin from the reference drug were 4276.75 ng x h x mL(-1), 5578.12 ng x h x mL(-1), 419.89 ng/mL, and 51.23 h, respectively. The median tmax of he test drug and reference drug were 3.0 h and 2.0 h, respectively. The geometric mean ratios (90% CI) of the test drug/reference drug for azithromycin were 101.56% (86.61-119.08%) for AUCt, 101.27% (84.97-120.70%) for AUCinf, and 97.78% (84.50-113.16%) for Cmax. Based on this study, it was concluded that the two azithromycin tablets (test and reference drug) were bioequivalent in terms of the rate and extent of absorption.

Bioequivalence assessment of two formulations of celecoxib: Open label, single dose and two-way cross over study in healthy human male volunteers

“…The acceptance criteria for bioequivalence were that the 90% Cls of the geometric mean ratios 0.80 to 1.25 for the AUC and Cmax. The tmax difference was analyzed non-parametrically on the original data using Wilcoxon matched-pairs test (Setiawati et al, 2009). …”

Validated HPLC‐UV method for determination of naproxen in human plasma with proven selectivity against ibuprofen and paracetamol

“…Sample pretreatment in the previous studies was based on solid‐phase extraction (Gopinath et al ., ; Patel et al ., ), protein precipitation (Bae et al ., ; Elsinghorst et al ., ; Helmy and El Bedaiwy, ; Martín et al ., ; Palma‐Aguirre et al ., ; Sakaguchi et al ., ; Sultana et al ., ; Xiong et al ., ) and liquid–liquid extraction (Carrasco‐Portugal et al ., ; Marzo et al ., ; Niazi et al ., ; Setiawati et al , ; Shimek et al ., ; Sun et al ., ; Yilmaz et al ., ; Toothaker et al ., ). Solid‐phase extraction methods are very effective and provide a selective cleanup, but they require the use of expensive instruments and cartridges.…”

“…The majority of methods for naproxen quantification in human plasma or serum samples are based on high‐performance liquid chromatography technique (HPLC) with various detections, such as chemiluminescent (Xiong et al ., ), fluorometric (Sakaguchi et al ., ; Shimek et al ., ; Toothaker et al ., ), mass spectrometric (Choi et al ., ; Elsinghorst et al ., ; Gopinath et al ., ; Patel et al ., ) and the most common ultraviolet (UV) (Bae et al ., ; Carrasco‐Portugal et al ., ; Helmy and El Bedaiwy, ; Martín et al ., ; Marzo et al ., ; Niazi et al ., ; Palma‐Aguirre et al ., ; Setiawati et al ., ; Sultana et al ., ; Sun et al ., ; Yilmaz et al ., ). For the HPLC‐UV assays the lowest reported lower limit of quantitation (LLOQ) value is 100 ng/mL (Sun et al ., ; Yilmaz et al ., ).…”

Naproxen: An Update on Physicochemical, Analytical and Pharmacological Aspects

“…When the drug is given in the presence of food, the peak plasma levels in most subjects are achieved in about 12 h [74]. However in such a situation, the time to achieve peak concentration gets reduced.…”