Drug release from an oromucosal paste for the selective decontamination of the oropharynx (in ICU patients and healthy volunteers)

Abstract

Selective oropharyngeal decontamination (SOD) is used in many ICUs in the Netherlands and some other European countries. While its clinical effect has been studied intensively, no studies have been done to assess the biopharmaceutical aspects of the paste, i.e. it is not known which local concentrations exist. For this study, five healthy volunteers were subjected to 400mg of the generally used paste. Ten ICU patients were treated according to the normal standard in the ICU of the University Medical Center Utrecht. Salivary levels of the various substances were measured over time using two separate analytical methods. Also the microbial burden of the oropharynx was assessed. The results show significant variation in release, both ICU patients and healthy volunteers. The antimicrobials tobramycin and colistin showed a relatively fast release, while nystatin exhibited a controlled release-like pattern. Amphotericin B is hardly released from the formulation. The concentration of the antimicrobial agents drop to sub-MIC levels relatively fast. From a biopharmaceutical perspective, amphotericin B should be replaced by nystatin. The application of the mouth paste is subject to massive variation in daily practice; each nurse applies a different amount, in a different way. In addition, the formulation is hard to apply and unpleasant with regards to the taste and feel for the conscious patients. This is not a clinical study, but a study that aimed to give a biopharmaceutical justification for SOD Both the clinical practice and the clinically determined levels of drugs enable critical evaluation of the outcome of clinical studies performed until now.