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.
BACKGROUND
The 2004 FDA ban on ephedra‐containing dietary supplements produced an upsurge of “ephedra‐free” products onto the U.S. market. Despite their “ephedra‐free” designation, many of these supplements contain botanical ingredients with sympathomimetic properties (e.g. synephrine, caffeine) that when taken together may produce untoward cardiovascular effects. The purpose of this study was to examine the cardiovascular and electrocardiographic effects of a 3‐day course of an “ephedra‐free” dietary supplement (Metabolife Ultra™).
METHODS
Baseline assessments of blood pressure were determined for 10 healthy male volunteers, and electrocardiographic data was collected for 24 hours via Holter monitoring. 24 hours later, subjects began a 3‐day regimen of Metabolife Ultra™ (2 tablets, 3 times daily). On the third day of supplementation, blood pressure and Holter monitoring were performed again. After a two‐week washout period, blood pressure and Holter monitoring were performed a third time. Group means for QTc, systolic and diastolic blood pressure, and heart rate were compared by nonparametric repeated measures ANOVA.
RESULTS
During supplementation, statistically significant increases were noted for QTc (+14 msec, p=0.04), systolic (+8 mm Hg, p=0.04), and diastolic blood pressure (+10 mm Hg, p<0.001). Two subjects exhibited prolongations in QTc intervals exceeding 40 milliseconds.
CONCLUSIONS
Metabolife Ultra™ may cause clinically significant changes in cardiac indices.
Clinical Pharmacology & Therapeutics (2005) 79, P2–P2; doi:
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