Pharmacokinetics of ciprofloxacin as a tool to optimise dosage schedules in community patients.
OBJECTIVE
To evaluate the dosage regimens of ciprofloxacin prescribed for outpatients by applying the principles of antibacterial therapy.


METHODS
Retrospective analysis of prescription and demographic data.


METHODS
Community pharmacy in Valladolid, Spain.


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


METHODS
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.


RESULTS
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 Cmax /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 Cmax /MIC and AUC24 /MIC ratios lower than those associated with clinical efficacy and minimal spread of bacterial resistance.


CONCLUSIONS
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 Cmax /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.
Sánchez Navarro
M Dolores
MD
Community Pharmacy from Valladolid, Spain.
Coloma Milano
Carlos
C
Zarzuelo Castañeda
Aránzazu
A
Sayalero Marinero
M Luisa
ML
Sánchez-Navarro
Amparo
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood* / Q000652:urine*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000097:blood* / Q000652:urine*; D004334:Drug Administration Schedule; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010031:Otitis / Q000097:blood / Q000188:drug therapy / Q000652:urine; D010045:Outpatients; D011472:Prostatitis / Q000097:blood / Q000188:drug therapy / Q000652:urine; D012141:Respiratory Tract Infections / Q000097:blood / Q000188:drug therapy / Q000652:urine; D012189:Retrospective Studies; D014552:Urinary Tract Infections / Q000097:blood / Q000188:drug therapy / Q000652:urine
D000890:Anti-Infective Agents; D002939:Ciprofloxacin