Journal of Bioequivalence & Bioavailability

Single-Dose, Bioequivalence, Rate of Absorption, and Food Effect Study of a New Paracetamol/Caffeine Formulation in Healthy Volunteers

2^nd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit-2011 and International Conference on Pharmaceutics & Novel Drug Delivery Systems

06-08 June 2011, Las Vegas, USA

Dongzhou J. Liu

Scientific Tracks Abstracts: JBB

Abstract:

T o determine the relative bioavailability and bioequivalence in fasted and semi- fed states, and compare the rate and extent of absorption and food eff ect of two formulations of paracetamol + caff eine products: Panadol Extra (currently-marketed product) and Panadol Extra Advance. Th is study was designed as a single-center, open-label, randomized, single-dose, 4-way (2 formulations and 2 food states) crossover study. In each period, two caplets of either Extra Advance or current Extra, each totaling 1000 mg paracetamol + 130 mg caff eine, were orally administered. Th irty subjects were enrolled with all completing the study. Serial blood samples were collected at pre-dose until 10-hours post-dose. Plasma samples were assayed for paracetamol and caff eine concentration using HPLC/MS methods. Pharmacokinetic parameters were computed using a non-compartmental model. A linear mixed-eff ect model was used to analyze the logarithmically transformed AUC 0-∞ , AUC 0-t and C max as well as AUC 0-30min and AUC 0-60min . T max was analyzed by a signed rank test on the within-subject diff erences. Th e new formulation was well tolerated by the subjects. For both paracetamol and caff eine, the 90% confi dence intervals for the ratios of AUC 0-∞ , AUC 0-t , and C max for Extra Advance and current Extra, in both fasted and semi-fed states, all lied within the bioequivalence boundaries of [0.80, 1.25], except for paracetamol C max in the fasted state, which was [1.11, 1.30] (mean ratio was 1.20). Th e new formulation showed signifi cantly greater early absorption (AUC 0-30min and AUC 0- 60min ) for both paracetamol and caff eine compared to Panadol Extra (P<0.0001) in both fasted and semi-fed states (ratios in the range of 1.4 to 7.7). Th e new formulation showed signifi cantly shorter T max for both paracetamol and caff eine (P<0.05), and paracetamol T 4 (time to reach minimum therapeutic concentration in plasma of 4μg/ ml) was twice as fast as Panadol Extra in both fasted and fed states. Th e new Panadol Extra Advnace formulation is bioequivalent to the currently marketed Panadol Extra formulation. Both paracetamol and caff eine are absorbed signifi cantly faster with the new formulation compared to Panadol Extra.

Biography :

Dr. Dongzhou (Jeffery) Liu is working at GlaxoSmithKline as Medical Lead/Principal Clinical Investigator. Previously, he worked at Wyeth (now P fi zer) and Forest Labs with increasing responsibilities. His past 13 years? industry experiences include pharmaceutical, preclinical, and clinical development of medical products with making key contribution in launching 7 marketed Rx drug products. The areas of his expertise include ADME/PK/BE/BA study, PK/PD modeling & simulation, IVIVC/IVIVE/IVMS, innovative drug design and delivery, Biopharmaceutical pro fi ling. He obtained a PhD in Biochemistry, a MS in computer sciences, and a BS in Chemistry. He also obtained a EMBA. He has more than 50 publications and presented 20+ keynote speeches at global conferences. He is the lecture professor at SUNY-Old Westbury and Tianjin University School of Pharmacy. He is the members of NYAS, AAPS, ISSX, ACS, SAPA, etc.