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Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier disruption as measured by microdialysis.

Yang FY, Lin YL, Chou FI, Lin YC, Hsueh Liu YW, Chang LW, Hsieh YL - PLoS ONE (2014)

Bottom Line: With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater.This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site.Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.

ABSTRACT
The blood-brain barrier (BBB) can be transiently disrupted by focused ultrasound (FUS) in the presence of microbubbles for targeted drug delivery. Previous studies have illustrated the pharmacokinetics of drug delivery across the BBB after sonication using indirect visualization techniques. In this study, we investigated the in vivo extracellular kinetics of boronophenylalanine-fructose (BPA-f) in glioma-bearing rats with FUS-induced BBB disruption by microdialysis. After simultaneous intravenous administration of BPA and FUS exposure, the boron concentration in the treated brains was quantified by inductively coupled plasma mass spectroscopy. With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater. This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site. Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

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Related in: MedlinePlus

The boron concentration versus time profiles in the dialysate of the plasma after BPA administration at 500/kg in glioma-bearing rats with or without FUS exposure.The concentration of boron measured in each 15-min sample of plasma represents the average concentration of that interval. Data are expressed as mean ± SEM, n = 6.
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pone-0100104-g001: The boron concentration versus time profiles in the dialysate of the plasma after BPA administration at 500/kg in glioma-bearing rats with or without FUS exposure.The concentration of boron measured in each 15-min sample of plasma represents the average concentration of that interval. Data are expressed as mean ± SEM, n = 6.

Mentions: The concentration versus time curves for boron in plasma before and after intravenous injection both with and without FUS exposure were almost identical (Fig. 1). The mean peak values were similar to those of the concentration profiles, in which the highest boron accumulation in the brain tumor ECF occurred at 30 min after drug injection and declined rapidly during the elimination phase.


Pharmacokinetics of BPA in gliomas with ultrasound induced blood-brain barrier disruption as measured by microdialysis.

Yang FY, Lin YL, Chou FI, Lin YC, Hsueh Liu YW, Chang LW, Hsieh YL - PLoS ONE (2014)

The boron concentration versus time profiles in the dialysate of the plasma after BPA administration at 500/kg in glioma-bearing rats with or without FUS exposure.The concentration of boron measured in each 15-min sample of plasma represents the average concentration of that interval. Data are expressed as mean ± SEM, n = 6.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061112&req=5

pone-0100104-g001: The boron concentration versus time profiles in the dialysate of the plasma after BPA administration at 500/kg in glioma-bearing rats with or without FUS exposure.The concentration of boron measured in each 15-min sample of plasma represents the average concentration of that interval. Data are expressed as mean ± SEM, n = 6.
Mentions: The concentration versus time curves for boron in plasma before and after intravenous injection both with and without FUS exposure were almost identical (Fig. 1). The mean peak values were similar to those of the concentration profiles, in which the highest boron accumulation in the brain tumor ECF occurred at 30 min after drug injection and declined rapidly during the elimination phase.

Bottom Line: With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater.This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site.Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei, Taiwan.

ABSTRACT
The blood-brain barrier (BBB) can be transiently disrupted by focused ultrasound (FUS) in the presence of microbubbles for targeted drug delivery. Previous studies have illustrated the pharmacokinetics of drug delivery across the BBB after sonication using indirect visualization techniques. In this study, we investigated the in vivo extracellular kinetics of boronophenylalanine-fructose (BPA-f) in glioma-bearing rats with FUS-induced BBB disruption by microdialysis. After simultaneous intravenous administration of BPA and FUS exposure, the boron concentration in the treated brains was quantified by inductively coupled plasma mass spectroscopy. With FUS, the mean peak concentration of BPA-f in the glioma dialysate was 3.6 times greater than without FUS, and the area under the concentration-time curve was 2.1 times greater. This study demonstrates that intracerebral microdialysis can be used to assess local BBB transport profiles of drugs in a sonicated site. Applying microdialysis to the study of metabolism and pharmacokinetics is useful for obtaining selective information within a specific brain site after FUS-induced BBB disruption.

Show MeSH
Related in: MedlinePlus