Pharmacokinetics of Ciprofloxacin as a Tool to Optimise Dosage Schedules in Community Patients

To evaluate the dosage regimens of ciprofloxacin prescribed for outpatients by applying the principles of antibacterial therapy.

Retrospective analysis of prescription and demographic data.

Community pharmacy in Valladolid, Spain.

Fifty male and female patients aged 18–93 years and with bodyweight 41–95kg.

Prescribed dosage regimen, age, weight, height, type of infection, comorbidity and coadministered drugs were recorded for each patient. Plasma concentration curves were simulated from literature values of the pharmacokinetic parameters of the drug and the age and weight of the patients. Urine concentrations were estimated from simulated plasma concentrations, literature values of renal clearance and an average urinary flow rate of 2 L/day. The potential efficacy of the prescribed treatment was evaluated from the ratio of the simulated peak plasma concentration (C_max) to the literature value of the minimum inhibitory concentration (MIC) for the bacterium most probably responsible for the infection (C_max/MIC). The ratio of area under the plasma concentration-time curve over 24 hours to MIC (AUC₂₄/MIC) was also estimated for non-urinary infections.

Demographic variables such as age or bodyweight do not seem to be taken in consideration when ciprofloxacin is prescribed, at least in the patients considered here, leading to wide interindividual variability in plasma concentrations. This may not be relevant for urinary infections, since ciprofloxacin concentrates in the urine, leading to high C_max/MIC ratios in all patients. Simulated plasma concentration-time curves revealed consistent underdosing for systemic infections in young patients over 60kg, for whom the plasma concentrations achieved led to C_max/MIC and AUC₂₄/MIC ratios lower than those associated with clinical efficacy and minimal spread of bacterial resistance.

The standard regimen of ciprofloxacin 250mg every 12 hours prescribed for urinary infections may not be the best choice, since a more convenient regimen of 500mg once daily leads to a higher C_max/MIC ratio, which is associated with a more significant postantibiotic effect and higher efficacy of fluoroquinolones. For non-urinary infections, the age and weight of patients should be taken into account to achieve optimum plasma concentrations.