Abstract

EVALUATION OF BIOEQUIVALENCE AND PHARMACOKINETIC STUDIES OF TWO FORMULATION OF PARACETAMOL ER 650 MG IN HEALTHY INDIAN ADULT VOLUNTEERS

Rajendra. M. Kawade*, Kishor. B. Burade, Nitin. B. Ghiware,Sudhir. M Vadvalkar

ABSTRACT

PURPOSE: To compare the bioavailability and tolerability of 2 oral formulations of paracetamol ER 650 mg. METHODS: This single‐dose, randomized, single‐label, 2‐period crossover study in healthy Indian adult volunteers was conducted at Shree Hospital and ICU Pvt. Ltd. Karad, Dist. Satara, Maharashtra, India. Subjects received paracetamol ER 650 mg of either test or reference formulation with a washout period of 7 days. After study drug administration, serial blood samples were collected over a period of 24 hours. Plasma was analyzed for paracetamol concentration using a validated high‐performance liquid chromatography method. Pharmacokinetic (PK) parameters Cmax, Tmax, t1/2, AUC0‐t, AUC 0‐∞, and kel, were determined for the 2 paracetamol formulations. The formulations were to be considered bioequivalent if the log‐transformed ratios of Cmax, AUC0‐t, and AUC0‐∞ were within the predetermined bioequivalence range of 80% to 125%. RESULTS: A total of 18 subjects were enrolled (mean BMI 20.97, a mean age of 30.4 years, mean weight of 61.5 kg and a mean height of 167.6 cm). No significant differences were found based on analysis of variance, with mean values and 90% confidence intervals of test/reference ratios for these parameters as follows: Cmax, 7.02 versus 7.17 μg/mL (88.9‐108.9); AUC0‐t, 31.54 versus 32.12 μg. hr/mL (91.30‐103.1); and AUC0‐∞, 32.30 versus 32.70 μg. hr/mL (92.58‐107.6). CONCLUSION: In these healthy Indian volunteers, results from the PK analysis suggested that the test and reference formulations of paracetamol ER 650 mg tablets were bioequivalent, based on the regulatory definition.

Keywords: Paracetamol, Bioequivalence evaluation, Pharmacokinetics.