A Study Investigating the Absorption and Pharmacokinetics of a Newly Developed Paracetamol/Caffeine Formulation Containing Sodium Bicarbonate in Healthy Volunteers.
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Date
2013-10
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Abstract
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.
Description
Keywords
Paracetamol/acetaminophen, caffeine, sodium bicarbonate, bioequivalence, pharmacokinetics, rapid-release formulation, drug absorption
Citation
Liu Dongzhou J, Gupta Ashok, Allison Mark J. A Study Investigating the Absorption and Pharmacokinetics of a Newly Developed Paracetamol/Caffeine Formulation Containing Sodium Bicarbonate in Healthy Volunteers. British Journal of Pharmaceutical Research. 2013 Oct; 3(4): 839-853.