Distribution of ciprofloxacin in the peripheries

Abstract

The principal objective of this study was to develop and validate innovative, simple, rapid and effective High Performance Liquid Chromatography (HPLC) methods for the quantification of either ciprofloxacin or clindamycin, to be used in the blood and tissue of patients suffering from Peripheral Arterial Disease (PAD). The antibiotic used for this study was selected according to which suitable method of analysis could be developed and validated to be then used for high throughput screening in the local clinical setting. This method was used on blood and tissue samples of patients suffering from varying degrees of PAD. Other aims included evaluating factors influencing the distribution of the chosen antibiotic in the peripheries of patients suffering from PAD, establishing a 3-predictor regression model in relation to such a distribution and trying to predict the concentration of the chosen antibiotic present in the infected tissue. The regression model developed helped predict whether the chosen antibiotic reaches the infected area in concentrations which are high enough to treat the infection. Ciprofloxacin was chosen and innovative methods for its determination and quantification in blood and tissue were validated following method development. These methods were used to quantify ciprofloxacin in blood and tissue of patients suffering from PAD. Blood and tissue samples were collected from 50 patients (33 male; 17 female) who were admitted to hospital for debridement or amputation procedures. The majority of these patients (n= 49) were suffering from diabetes. Thirty- five patients were suffering from severe PAD. A 3-predictor regression model was developed from the data collected. It was found that the concentration of ciprofloxacin reaching the infected tissue was dependent on the severity of P AD, the number of medications that the patient was taking and on the concentration of ciprofloxacin in plasma. The regression model was then tested on samples of IO of these patients. The calculated value for ciprofloxacin concentrations obtained using the regression model was compared to the already determined ciprofloxacin concentration by HPLC. The regression model was also used on other blood samples of patients from whom debrided or amputated tissue samples could not be collected. This was done to help determine how much ciprofloxacin reached the ischemic peripheries. The innovative HPLC methods which were developed and validated for the determination of ciprofloxacin in plasma and tissue can be effectively used for high throughput analysis in a clinical setting where results can be attained in a short period of time for a large number of patient samples. The regression model developed can help predict and help calculate a more tailored individualised dose of ciprofloxacin for patients suffering from infections in the peripheries. This can lead to adequate dosing in these patients with less undesirable effects and better treatment outcomes avoiding unwanted complications and achieving higher levels of therapeutic success in the process. Keywords: ciprofloxacin, peripheral arterial disease, high performance liquid chromatography, blood, tissue