Abstract
Purpose: The published literature asserts that the individual pharmacokinetic parameters of ibuprofen and paracetamol are not altered following concurrent administration in a fasted state. The present study was performed to confirm these observations for a novel fixed dose oral combination (Maxigesic®) containing paracetamol 500 mg and ibuprofen 150 mg/tablet. Additionally, the effect of food on the pharmacokinetic profile of the Maxigesic® formulation was assessed. Methods: A single-dose, open-label, randomized, four-way crossover pharmacokinetic study was undertaken in 28 healthy volunteers. Serial plasma samples were assayed for both paracetamol and ibuprofen concentrations using validated LC-MS/MS methods. Ratios of Cmax, AUC0→t and AUC0→∞ were analysed for bioequivalence as determined by 90% confidence intervals (CI) and tmax values were compared using the Wilcoxon matched pairs test. Results: In the fasted state, pharmacokinetic parameters for ibuprofen and paracetamol were similar between the fixed dose combination and its mono-components. Ratios of Cmax, AUC0→12h, and AUC0→∞ values fell within the 80-125% acceptable bioequivalence range and tmax values were not altered significantly. In the fed state compared with the fasted state, the tmax from the fixed dose combination was significantly prolonged for paracetamol (53 vs 30 minutes) and slightly delayed for ibuprofen (53 vs 90 minutes). Slower absorption of paracetamol resulted in a reduced Cmaxwhich was outside the 80-125% bioequivalence range. Additionally, in the fed state, the extent of absorption of both paracetamol and ibuprofen from the fixed dose combination was slightly less compared with the fasted state, although the 90% CI for the AUC0→12h and AUC0→∞ ratios were within the 80-125% bioequivalence range. Conclusions: The concomitant administration of ibuprofen and paracetamol in a fixed dose combination (Maxigesic®) does not alter the pharmacokinetic profiles of either drug in the fasted state and there was no effect of food on the absorption from the fixed dose combination.
Highlights
MethodsA single-dose, open-label, randomized, four-way crossover pharmacokinetic study was undertaken in 28 healthy volunteers
The concomitant administration of ibuprofen and paracetamol in a fixed dose combination (Maxigesic®) does not alter the pharmacokinetic profiles of either drug in the fasted state and there was no effect of food on the absorption from the fixed dose combination
Previous bioequivalence studies conducted with other fixed dose combination products containing paracetamol 650 mg and ibuprofen 400 mg [2] and paracetamol 1000 mg and ibuprofen 400 mg [3] found that the addition of ibuprofen to paracetamol resulted in an increase in the rate of absorption of the latter
Summary
A single-dose, open-label, randomized, four-way crossover pharmacokinetic study was undertaken in 28 healthy volunteers. Ratios of Cmax, AUC0→t and AUC0→∞ were analysed for bioequivalence as determined by 90% confidence intervals (CI) and tmax values were compared using the Wilcoxon matched pairs test. This study was a Phase 1, single-centre, open-label, randomized, single-dose, four-way crossover trial in 28 healthy adult participants. Plasma concentrations of paracetamol and ibuprofen in human plasma (Li-heparin) were determined using validated Liquid. The pharmacokinetic calculations were performed using the computer program KineticaTM 2000. The ratios of the geometric means used to test bioequivalence were calculated from loge transformed data for Cmax, AUC0→t and AUC0→∞. Tmax was compared between formulations and fast/fed states using the Wilcoxon signed rank test and the median differences and 95% CIs were determined using Hodges-Lehman estimates.
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