Relative bioavailability of new formulation of paracetamol effervescent powder containing sodium bicarbonate versus paracetamol tablets: a comparative pharmacokinetic study in fed subjects.
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 microg/ml. The quantification limit was 0.2 microg/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.


CONCLUSIONS
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.
Di Girolamo
Guillermo
G
Second Chair of Pharmacology, Universidad de Buenos Aires, Department of Pharmacology, School of Medicine, Ciudad Autónoma de Buenos Aires, Argentina. gdigirolamo@arnet.com.ar
Opezzo
Javier A W
JA
Lopez
Marcela I
MI
Schere
Daniel
D
Keller
Guillermo
G
Gonzalez
Claudio D
CD
Massa
Javier Martinelli
JM
de los Santos
María Cecilia
MC
D000082:Acetaminophen / Q000737:chemistry* / Q000493:pharmacokinetics*; D000328:Adult; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D005260:Female; D005502:Food; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011208:Powders; D017693:Sodium Bicarbonate / Q000737:chemistry* / Q000493:pharmacokinetics*; D013607:Tablets
D011208:Powders; D013607:Tablets; D000082:Acetaminophen; D017693:Sodium Bicarbonate