A Study Investigating the Absorption and Pharmacokinetics of a Newly Developed Paracetamol/Caffeine Formulation Containing Sodium Bicarbonate in Healthy Volunteers
Dongzhou J. Liu, Ashok Gupta, Mark J. Allison
Journal of Pharmaceutical Research International · pp. 839–853 · Published 16 Jul 2013
10.9734/BJPR/2013/4104Abstract
Aims: To assess pharmacokinetic (PK) bioequivalence between a newly developed formulation, rapid-relese paracetamol plus sodium bicarbonate and caffeine (RAPC), containing 500 mg paracetamol + 65 mg caffeine + 325 mg sodium bicarbonate), and the currently marketed Panadol® Extra product in both the fasted and semi-fed states. Study Design: A single center, randomized, open label, four-way crossover, PK study. Place and Duration of Study: MDS Pharma Services (Now Celerion), 2420, W. Baseline Road, Tempe, AZ 85283, between July 17, 2009 to August 10, 2009. Methodology: We included 30 healthy volunteers (20 males, 10 females; age range 18-55 years). The characterized PK parameters included total and partial area under the concentration time curve (AUC0-30min, AUC0-60min, AUC0-t/AUC0-∞), time to reach peak drug plasma concentration/therapeutic level (Tmax/Tc≥4ug/ml), and maximum measured plasma concentration (Cmax). The safety of the study treatments was also assessed. Results: In both fasted and semi-fed states, the exposure to paracetamol and caffeine for new RAPC formulation was bioequivalent to Panadol® Extra for AUC0-10 hrs, AUC0-∞ and Cmax with 90% confidence intervals (CIs), all being within the range 0.80 to 1.25, except for a higher paracetamol Cmax for RAPC in fasted state. RAPC exhibited significantly greater early absorption for both paracetamol (≥1.8-fold greater) and caffeine (≥1.3-fold greater) as determined by AUC0-30min and AUC0-60min, as well as significantly faster Tmax for both paracetamol (about 30 minutes faster) and caffeine (≥15 minutes faster) compared to currently marketed Panadol® Extra in both fasted and semi-fed states. The time to reach the therapeutic paracetamol plasma concentration (Tc≥4µg/ml) was about 12 and 33 minutes faster in fasted and semi-fed states respectively. The new formulation was safe and well tolerated. Conclusion: The newly developed RAPC formulation was found to be bioequivalent to Panadol® Extra caplets, and showed significantly faster absorption in both fasted and semi-fed states.
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