title: Pharmacokinetic and bioequivalence studies of immediate release diclofenac potassium tablets (50mg) in healthy volunteers.
abstract: This study was conducted with the aim to determine the pharmacokinetic and bioequivalence of diclofenac potassium 50 mg test (F4) tablet formulation with reference product (Caflam). Present study was single dose, randomized, two phase cross over design, conducted in 12 healthy Pakistani volunteers and planned in accordance with FDA guidelines. In this study a simple, selective, sensitive and reproducible HPLC procedure was developed and validated for the estimation of diclofenac potassium in plasma. The process was validated in the range of 50 - 0.05 µg.mL-1 and used in bioequivalence trial of two products. Multiple blood samples were collected at various time points (0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 14 hr after treating volunteers with test (F4) and marketed reference brand. Plasma separation and deproteination were carried out with acetonitrile; samples (20µL) were injected using the validated HPLC method. Various pharmacokinetic parameters (compartmental and noncompartmental) were estimated using KineticaTM 4.4.1 (Thermo Electron Corp. USA). Bioequivalence among the products was established by calculating the 90% CI with log and non log transformed data for Cmaxcalc, Tmaxcalc, AUC0-∞, AUCtot and AUClast using two way ANOVA and Schirmann's Two one sided t- test. No significant difference was found between log and non-log data. The 90% confidence interval values using log transformed data for AUC0-∞ (0.997-1.024), AUCtot (1.004-1.031), AUClast (0.997 -1.024), Cmaxcalc (0.994-1.007) and Tmaxcalc (0.996-1.013) for the trial and reference products were found within the FDA acceptable limits of 0.8-1.25. Results were further verified by the Schirmann's one-sided t test. Results showed the bioequivalence of test and reference formulations. Both the products were well tolerated.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan / Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan.
authors.forename: Huma
authors.initials: H
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan.
authors.forename: Muhammad Harris
authors.initials: MH
authors.lastname: Shoaib
authors.affiliation: Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan.
authors.forename: Farya
authors.initials: F
authors.lastname: Zafar
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hanif
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan.
authors.forename: Rabia
authors.initials: R
authors.lastname: Bushra
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Karachi, Pakistan.
authors.forename: Asia
authors.initials: A
authors.lastname: Naz
authors.affiliation: Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan.
authors.forename: Raheela
authors.initials: R
authors.lastname: Khursheed
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010154:Pakistan; D012995:Solubility; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac