Enhanced oral bioavailability of vancomycin in rats treated with long-term parenteral nutrition

Abstract

Long-term parenteral nutrition (PN) can induce intestinal atrophy, leading to a loss of epithelial integrity in the small intestines. This change may alter the intestinal permeability of vancomycin (VCM), a non-absorbable antibiotic. The aim of the present study was to investigate the effect of PN on the pharmacokinetics of VCM in rats. VCM was intravenously (5 mg/kg) or intraduodenally (20 mg/kg) administered to control and PN rats, which were prepared by administration of PN for 9 days. After intravenous administration, there were no significant differences in any of the VCM pharmacokinetic parameters between the control and PN rats. However, after intraduodenal administration, the maximum concentration and area under the plasma concentration–time curve of VCM in PN rats was approximately 2.4- and 2.6-fold higher, respectively, than in the control rats; the calculated bioavailability was approximately 0.5 and 1.3 % in control and PN rats, respectively. These results indicated that PN administration did not affect VCM disposition, but enhanced VCM absorption; however, the enhanced oral VCM bioavailability was statistically, not clinically, significant. Therefore, while long-term PN administration may play a role in the enhancement of VCM bioavailability, this effect may be negligible without any complications.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-1228-8) contains supplementary material, which is available to authorized users.

Electrochemical Aptamer-Based Sensors for Improved Therapeutic Drug Monitoring and High-Precision, Feedback-Controlled Drug Delivery

“…Using KDM-corrected sensors can measure 9 s-resolved plasma vancomycin levels in real time after, for example, the intravenous injection of human-equivalent, 30 mg kg –1 doses (Figure B). The resultant pharmacokinetic curves obtained from this experiment produces peak concentrations and plasma half-lives consistent with values reported in the literature . The typical ∼15 min time resolution of these prior (research, not clinical) measurements, however, is poorly matched to the metabolic timescale of the drug, and thus the precision with which they define its distribution (α) and elimination (β) time constants is limited .…”

“…The resultant pharmacokinetic curves obtained from this experiment produces peak concentrations and plasma half-lives consistent with values reported in the literature. 41 The typical ∼15 min time resolution of these prior (research, not clinical) measurements, however, is poorly matched to the metabolic timescale of the drug, and thus the precision with which they define its distribution (α) and elimination (β) time constants is limited. 26 In contrast, high-frequency E-AB measurements return parameter estimates with precision (defined as 95% confidence intervals) of better than 20%, which is more than sufficient to identify statistically significant pharmacokinetic differences between individual animals (Figure 4B).…”

A microbial metabolite remodels the gut-liver axis following bariatric surgery

“…In vitro antibiotic treatment Based on the assumption that a mouse weighs approximately 30 g drinks 8 mL water/day (Bachmanov et al, 2002), we calculated that the antibiotic-treated sham and SG mice drank 6mL water/day on average. Next, based on the bioavailability of the antibiotics used (ampicillin, 1 g/L bioavailability = 50 %; vancomycin, 0.5 g/L bioavailability = 0.5 %; metronidazole, 0.25 g/L bioavailability = 90 %; and neomycin, 1 g/L bioavailability = 3 %) (Fukushima et al, 2015;Lamp et al, 1999), we calculated the amount of daily antibiotic exposure to which mouse tissues would be exposed: Cells were incubated in media containing 3 mg ampicillin, 0.015 mg vancomycin, 1.35 mg metronidazole, and 0.18 mg neomycin (along with the standard 100 units/mL penicillin, and 100 mg/mL streptomycin) for 16 h prior to cell viability assay or RNA extraction for qPCR.…”

Formulation of pH-Responsive Quatsomes from Quaternary Bicephalic Surfactants and Cholesterol for Enhanced Delivery of Vancomycin against Methicillin Resistant Staphylococcus aureus

“…The lowering of the MIC value of VCM shows the translational potential of this system without compromising the therapeutic effect of the loaded drug. This could lead to a reduction in the dose-dependent side effects of VCM, such as nephrotoxicity and Redman Syndrome [100]. Fluorescence microscopy was also used to investigate the quatsomes' ability to eliminate biofilms.…”