Pharmacokinetics of antimicrobial drugs in the cerebrospinal fluid.

The physicochemical properties of the blood-to-brain barrier, the cerebrospinal fluid (CSF) to brain barrier, and the blood-CSF barrier, including their specific transport mechanisms, are responsible for drug concentration time courses in the CSF, which increase slower and remain lower than in the serum. From the kinetic point of view the central nervous system (CNS) can be understood as a deep compartment in the organism. During the initial inflammatory phase of a bacterial meningitis, the penetration of antibiotics can be increased. Consequently, sufficient CSF concentrations should be achieved as soon as possible. To investigate the influence of the dosage regimen on the kinetic profile of antibiotics in the CSF, chloramphenicol and cefotaxim were measured using high pressure liquid chromatography (HPLC)-techniques. Five children had a bacterial meningitis and five an external ventricular drainage due to various diseases. Neither continuous infusion over a 12-24-hour-period nor four bolus-injections per day led to sufficient antimicrobial concentrations within the first hours after starting therapy. Using a loading dose of 40-50% of the daily dose administered over a 2-4-hour infusion period and followed by bolus injections, sufficient concentrations of chloramphenicol and cefotaxim could be achieved within a few hours. Besides an adequate choice of antibiotics, the special pharmacokinetic properties of the cerebrospinal membranes should not be neglected in the concept of the antibiotic therapy of meningitis.