title: A new high-absorption-rate Paracetamol 500-mg formulation: a comparative bioavailability study in healthy volunteers.
abstract: BACKGROUND
  Paracetamol is often the analgesic or antipyretic of choice, especially for patients for whom salicylates or other nonsteroidal anti-inflammatory drugs are contraindicated.
  
  
  OBJECTIVE
  The aim of this study was to compare the absorption rate of a new tablet formulation of paracetamol (500 mg) with a reference formulation of paracetamol at the same dose.
  
  
  METHODS
  This was a single-center, Phase I, open-label, randomized, 2-period, crossover, single-dose, comparative bioavailability clinical trial. During both study periods, healthy volunteers were given a single oral dose of a more hydrophilic test formulation of paracetamol, or a reference formulation. Fifteen plasma samples were obtained to determine paracetamol concentrations and to calculate kinetic parameters.
  
  
  RESULTS
  The study participants comprised 24 healthy volunteers (12 men, 12 women; mean [SD] age, 22.8 [1.5] years). The pharmacokinetic parameters calculated for the test versus the reference formulation were as follows: median time to maximum concentration (Tmax), 0.42 versus 0.75 hour; mean (SD) maximum plasma drug concentration (Cmax), 9.85 (2.40) μg/mL versus 8.33 (2.22) μg/mL; and mean (SD) area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞), 30.16 (8.87) μg·h/mL versus 28.49 (8.57) μg · h/mL. The 90% CIs of the ratios were as follows: base e logarithm (Ln)-transformed Cmax, 105.08% to 137.59%; Ln-AUC0-∞, 102.02% to 110.43%; and the difference in Tmax, -0.375 to -0.085 hours.
  
  
  CONCLUSIONS
  The speed of release and absorption was statistically significantly higher with the test formulation compared with the reference one (evaluated using Tmax, Cmax, and Cmax/AUC parameters). This speed is especially important for a rapid analgesic or antipyretic effect.
authors.affiliation: Clinical Pharmacology Study Unit, Clinical Pharmacology Service, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Portolés
authors.affiliation: Clinical Pharmacology Study Unit, Clinical Pharmacology Service, Hospital del Aire, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Puerro
authors.affiliation: Clinical Pharmacology Study Unit, Clinical Pharmacology Service, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Terleira
authors.affiliation: Clinical Pharmacology Study Unit, Clinical Pharmacology Service, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: MCC-Analítica, Barcelona, Spain.
authors.forename: Maria-Cruz
authors.initials: MC
authors.lastname: Caturla
authors.affiliation: Belmac Laboratories S.A., Madrid, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Fernández
authors.affiliation: Clinical Pharmacology Study Unit, Clinical Pharmacology Service, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Vargas
keywords: bioavailability; clinical trial; healthy volunteers; paracetamol; pharmacokinetics