title: 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 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.
authors.affiliation: Second Chair of Pharmacology, Universidad de Buenos Aires, Department of Pharmacology, School of Medicine, Ciudad Autónoma de Buenos Aires, Argentina. gdigirolamo@arnet.com.ar
authors.forename: Guillermo
authors.initials: G
authors.lastname: Di Girolamo
authors.forename: Javier A W
authors.initials: JA
authors.lastname: Opezzo
authors.forename: Marcela I
authors.initials: MI
authors.lastname: Lopez
authors.forename: Daniel
authors.initials: D
authors.lastname: Schere
authors.forename: Guillermo
authors.initials: G
authors.lastname: Keller
authors.forename: Claudio D
authors.initials: CD
authors.lastname: Gonzalez
authors.forename: Javier Martinelli
authors.initials: JM
authors.lastname: Massa
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: de los Santos
mesh_terms: 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
chemical_list: D011208:Powders; D013607:Tablets; D000082:Acetaminophen; D017693:Sodium Bicarbonate