Effects of paracetamol on the pharmacokinetics of ciprofloxacin in plasma using a microbiological assay

Background and objective: Pharmacokinetic drug interactions may result in a decrease or increase in the oral bioavailability of some drugs. Therefore, coadministration of drugs should be avoided, or at least undertaken only when careful therapeutic drug monitoring is possible. Because of the common practice of coadministering paracetamol (acetaminophen) for fever in patients taking the antibacterial ciprofloxacin for infection, we investigated the influence of paracetamol on the pharmacokinetics of ciprofloxacin. Methods: In a randomised, two-way crossover study, 10 healthy male volunteers received a single oral dose of ciprofloxacin 500mg or ciprofloxacin 500mg plus paracetamol 500mg. Pharmacokinetic parameters were measured in plasma samples using a microbiological assay. Results: No significant differences were found as a result of concomitant administration of paracetamol in the ciprofloxacin pharmacokinetic parameters oral clearance (CL/F) and apparent volume of distribution (Vd/F). However, the ratio of the area under the concentration-time curves (AUCs) suggested that paracetamol increases ciprofloxacin concentrations on average by 16%. Concomitant administration of paracetamol slightly increased ciprofloxacin AUC(infinity) from 14.37 +/- 0.91 to 16.71 +/- 0.99 mu g . h/mL (p = 0.073) and ciprofloxacin maximum plasma concentration (C-max) from 2.52 +/- 0.18 to 2.61 +/- 0.24 mu g/mL (p = 0.113), while slightly decreasing time to ciprofloxacin Cmax from 1.5 to 1.3 hours (p 0.376). Conclusion: The results confirm an increased concentration-time profile of ciprofloxacin when the latter is coadministered with paracetamol. We believe that a pharmacokinetic interaction may have occurred.