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. DESIGN: Retrospective analysis of prescription and demographic data. SETTING: Community pharmacy in Valladolid, Spain. PATIENTS: 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.

Pharmacokinetic/pharmacodynamic modelling of ciprofloxacin 250 mg/12 h versus 500 mg/24 h for urinary infections.

A simulation study was performed to evaluate and compare the standard dosage regimen of 250 mg/12 h versus 500 mg/24 h of ciprofloxacin for the treatment of urinary tract infections (UTIs). Pharmacokinetic parameters reported for healthy young and old individuals were used for the simulation of drug levels in urine, at different mean urine flow rates (1-2.5 L/day). Pharmacokinetic/pharmacodynamic analysis of the results revealed that 500 mg ciprofloxacin once a day produced a more favourable profile in urine than 250 mg/12 h, particularly in the elderly, due to the slower elimination of the drug in this group of patients. Circadian rhythms were also considered for the simulation of drug levels in urine. According to the results, 500 mg once a day administered in the morning would be a better choice than 250 mg/12 h at least for uncomplicated UTI; nevertheless, clinical assays are needed to prove this hypothesis.

Atención farmacéutica en antibioterapia: fluoroquinolonas / Antibiotherapy pharmaceutical care: fluoroquinolones

El incremento progresivo de microorganismos resistentes causantes de infecciones de difícil tratamiento ha llevado a la implantación de diversos programas destinados a evitar el abuso y mal uso de los antibióticos, al ser ésta una causa directamente relacionada con la aparición de resistencias. El objetivo de este estudio ha sido el de evaluar las pautas posológicas de las fluoroquinolonas prescritas en el ámbito comunitario en relación con su potencial eficacia, así como establecer un protocolo de actuación farmacéutica destinado a prevenir y evitar los PRMs más probables para este grupo de fármacos. Para ello se ha aplicado una metodología, previamente descrita, basada en la simulación de curvas de niveles de fármaco en sangre u orina considerando la variabilidad famacocinética asociada a las características demográficas de los pacientes. Los resultados obtenidos demuestran que las pautas de dosificación prescritas corresponden a unos estándares preestablecidos, independientemente de la edad o peso del paciente para el que se prescribe la quinolona. En consecuencia, las concentraciones de fármaco simuladas difieren significativamente de unos casos a otros, lo que puede no tener trascendencia clínica en infecciones urinarias debido a las altas concentraciones alcanzadas en orina, pero sí en infecciones de otro tipo, ya que los niveles en plasma simulados para ciprofloxacino son, en algunos casos, inferiores a los recomendados para optimizar la eficacia del tratamiento y minimizar la aparición de resistencias (AU)

Progressive resistance emergence responsible for infections with complicated treatments has lead to the establishment of different types of programs aimed at controlling the misuse of these drugs since the latter has been related to the emerging resistance. The aim of this study was to evaluate the dosage patterns of the fluoroquinolone prescriptions for the community patients in relation with its potential efficacy as well as to establish a protocol to be applied at the community pharmacy to avoid the most probable FRM for this group of drugs. The methodology used has been previously described and, briefly, it consists in the simulation of the urine and plasma drug levels taking into account the variability in pharmacokinetics, according to the demographics of the patient.The results show that a standard dosage pattern is prescribed with no consideration of the age and body weight, leading to a significant inter-variability in the simulated levels of the drug. This may not show clinical implications for urinary infections since these drugs concentrate in urine and reach sufficiently high values in this fluid. Nevertheless, despite urine levels simulated plasma concentrations of ciprafloxacin are in some cases lower than the recommended values for improving efficacy and reducing resistance emergence (AU)