Fluctuations in vancomycin CNS tissue concentrations following intermittent and continuous infusions in the rat

Abstract

The purpose of this investigation was to compare the variability of vancomycin concentrations in the serum and CNS when administered continuously or as intermittent intravenous infusions in the rat. The hypothesis for this investigation was that the magnitude of change in serum vancomycin concentrations directly relates to the extent of vancomycin concentration fluctuations in the CNS. Microdialysis and serum sampling techniques were employed and biologic samples were analysed for vancomycin using HPLC. Over the dosing interval, the mean changes in concentrations were 71.8 +/- 9.8% and 13.6 +/- 9.3% for serum and 61.7 +/- 7.8% and 6.8 +/- 3.5% for brain extracellular fluid in the intermittent and continuously infused groups, respectively. Accordingly, the relative changes in vancomycin concentrations in brain extracellular fluid were closely associated with corresponding changes in serum concentrations (R2=0.94). Thus, continuous intravenous administration of vancomycin results in minimal serum and CNS tissue concentration changes as compared to traditional intermittent dosing methods and allows for more consistent vancomycin concentrations in the CNS.

Successful management of discovered pH dependence in vancomycin recovery studies: novel HPLC method for microdialysis and plasma samples

“…Table 2. Maximum within-and between-day imprecision (expressed as coefficient of variation, CV, %) and inaccuracy (expressed as mean percentage deviation, RE, %) of determined vancomycin concentrations (µ µ µ µ µg/mL) in plasma Luer et al (2004) was used under in vitro conditions using a flow rate of 1.7 µL/min and Ringer's solution as perfusate. Changing additionally the concentration in the perfusate from 1 to 80 µg/mL led to RR changes of more than 30%.…”

Underestimation of rat serum vancomycin concentrations measured by an enzyme‐multiplied immunoassay technique and the strategy for its avoidance

“…However, administration of VCM carries a considerable risk of causing adverse events including nephrotoxicity in spite of excellent antimicrobial efficacy, and this increased risk is dependent on the characteristics of VCM's disposition associated with the degree of its systemic exposure. In these experiments, VCM concentrations in rat serum or plasma were measured by means of various analytical techniques such as fluorescence polarization immunoassay (FPIA), [10][11][12][13][14][15][16][17][18] high performance liquid chromatography (HPLC), [19][20][21][22][23][24][25] liquid chromatography-mass spectrometry (LC-MS), [26,27] and bioassay. [9] From these aspects, a number of pharmacokinetic studies of VCM using rats have been extensively conducted to provide supportive evidence for promoting the appropriate and improved use of this drug.…”