Antonio Portolés1, Miguel Puerro2, Ana Terleira1, Angel Rodríguez1, Maria-Cruz Caturla3, Nieves Fernández4, Emilio Vargas1. 1. Clinical Pharmacology Study Unit, Clinical Pharmacology Service, Hospital Clínico San Carlos, Madrid, Spain. 2. Clinical Pharmacology Study Unit, Clinical Pharmacology Service, Hospital del Aire, Madrid, Spain. 3. MCC-Analítica, Barcelona, Spain. 4. Belmac Laboratories S.A., Madrid, Spain.
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.
RCT Entities:
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.
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