Relative bioavailability of new formulation of paracetamol effervescent powder containing sodium bicarbonate versus paracetamol tablets: a comparative pharmacokinetic study in fed subjects

Abstract

Objective: the aim of this relative bioavailability study was to determine the rate and extent of absorption of Alikal Dolor^® (effervescent powder containing paracetamol 500 mg/sodium bicarbonate 2318 mg) – test formulation (T) in relation to Parageniol^® (paracetamol 500 mg coated tablets) – reference formulation (R). Methods: 18 healthy volunteers (10 male and 8 female aged between 21 and 46 years) received, after 2 h of standardized breakfast, a single oral dose with 220 ml of water, in an open, randomized, crossover study, with a 7-day wash-out period. Paracetamol concentrations were established at 0, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 75, 90 min and at 2, 4, 6, 8 and 10 h postdose by HPLC with an ultraviolet detector. Results: the regression coefficient determined for paracetamol calibration curves was 0.9983 ± 0.0034 and the working range was from 0.2 to 50 μg/ml. The quantification limit was 0.2 μg/ml. The rate of absorption was significantly greater (p < 0.03) for T (T_max = 20.4 min) compared with R (T_max = 38.4 min). Extent of absorption over the first 30 min postdose AUC_{(0-30 min)} was 4.21-fold greater (p < 0.03) for T compared with R, without differences between C_max. The 90% CI on the geometric mean for C_max, AUC_{(0-10 h)} and AUC_(0-∞) ratios (T/R) were within the limits of 0.80 – 1.25, indicating both formulations were bioequivalent with respect to these parameters. Conclusion: paracetamol was absorbed at least twice as fast from T-containing sodium bicarbonate compared with R. This pharmacokinetic feature could prove crucial from the therapeutic point of view as it would allow a lower latency in the action time of paracetamol in producing its analgesic and antithermal effect.

Keywords::

• bioavailability
• effervescent
• paracetamol tablet
• pharmacokinetic
• sodium bicarbonate

Disclosure

This study was supported by GlaxoSmithKline Consumer Healthcare Argentina, South America.

The authors would like to thank P Czerniuk and R Bertuola for their professional participation during the hospitalization of the volunteers, JC Vassallo for his technical support and MB Kramer for study monitoring and administrative assistance.