PubMed Health⌕ Search

Biomedical subjects

D E Burgio

Publications and source records attributed to D E Burgio.

6 recordsLinked to original sources
PubMed1998

Inhibition of brain choline uptake by isoarecolone and lobeline derivatives: implications for potential vector-mediated brain drug delivery.

Delivery of certain compounds to brain is restricted by the nature of the blood-brain barrier (BBB). Many valuable pharmaceuticals are excluded from the CNS due to hydrophilicity or charge. These limitations have been overcome by numerous methods. One method we use is to take advantage of saturable nutrient transporters located at the barrier. These systems transport hydrophilic and charged nutrients into brain such as choline, a quaternized neurotransmitter precursor. Using knowledge of their substrate specificity, it is possible to deliver agents into brain using these nutrient carriers. In this report, derivatives of lobeline and isoarecolone were evaluated to determine if they may gain access to brain by the blood-brain barrier basic amine transporter using the in situ brain perfusion technique. These compounds do bind the blood-brain barrier basic amine transporter and may enter brain by this transport system.

Animals↗
PubMed1998

Effects of P-glycoprotein modulators on etoposide elimination and central nervous system distribution.

In this study, P-glycoprotein modulator effects on pharmacokinetics and central nervous system distribution of the chemotherapeutic agent etoposide were evaluated. The multidrug resistance transporter P-glycoprotein is expressed in normal tissues, and its physiological function is thought to be an excretory and/or protective one. To examine this further, we evaluated etoposide under steady-state and bolus dose conditions. In microdialysis infusion studies, etoposide 15 mg/kg/hr was administered to 12 rats. Rats received sodium cyanide (1 or 100 mM), trifluoperazine (30 mM) or cyclosporine (4.14 mM) via microdialysis probe at 3.5 hr after etoposide infusion initiation. High-dose sodium cyanide (100 mM) increased the etoposide BBR,corr from 0.09 +/- 0.03 to 0.85 +/- 0.35. Similarly, trifluoperazine significantly increased the BBR,corr (0.05 +/- 0.02 vs. 1.30 +/- 0.43), whereas cyclosporine had no effect. In bolus studies, etoposide (10-12 mg/kg) was given alone or concomitant to cyclosporine (5 mg/kg) or tamoxifen (13.5 mg/kg). Control etoposide total systemic clearance (ml/min/kg) was 29.3 +/- 13.0 vs. 16.0 +/- 1.9 and 22.6 +/- 5.3 for cyclosporine and tamoxifen treatments, respectively. Etoposide nonrenal clearance (ml/min/kg) values for cyclosporine (12.0 +/- 1.6) and tamoxifen (18.1 +/- 3.6) treatments was also decreased from controls (23.5 +/- 10.5). Etoposide renal clearance (ml/min/kg) values (5.7 +/- 2.5) were not significantly different from cyclosporine (4.0 +/- 0.7) or tamoxifen (4.6 +/- 1.7) treatments, respectively. In this study, the ability of sodium cyanide and trifluoperazine to alter etoposide BBR,corr, demonstrated that etoposide distribution into brain is partly controlled by an active transport process. Similarly, the results indicate cyclosporine inhibits etoposide transport at the canalicular membrane and/or etoposide P-450 metabolism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Modulation effects of cyclosporine on etoposide pharmacokinetics and CNS distribution in the rat utilizing microdialysis.

In the present study, we evaluated the pharmacokinetics of the chemotherapeutic agent etoposide (ET) under steady-state conditions and examined its extent of distribution into the CNS of conscious animals. An i.v. infusion of 15 mg/kg/hr was administered to nine rats. Each of the nine rats also received the potent multidrug resistance (MDR) modulator cyclosporine (CSA). Upon the addition of CSA, the i.v. treated animals demonstrated a 53% decrease in ET clearance. This decrease resulted in a greater than 2-fold increase in the steady-state concentrations of ET> The corrected brain-blood ratio (BBR (corr)) was 0.36 +/- 0.18 prior to CSA treatment, and although CNS concentrations increased upon the addition of CSA, there was no increase in the BBR(corr) (0.24 +/- 0.10). The present study demonstrates that the increase of ET in the CNS following CSA is a result of a decrease in ET systemic clearance and not an inhibition of ET efflux from the CNS.

Animals↗
PubMed1992

Antipyrine as a dialyzable reference to correct differences in efficiency among and within sampling devices during in vivo microdialysis.

Antipyrine was investigated as a dialyzable substance that could be used to quantitate relative differences in the efficiency of dialysis among multiple microdialysis probes and by a single probe over time. The contribution of effective membrane surface area to recovery variability was tested by the introduction of air into microdialysis probes. Reduction of effective membrane surface area reduced antipyrine recovery. Dialysates from probes implanted in the jugular vein, brain, and liver of rats receiving antipyrine demonstrated differences in antipyrine concentration among probes within the same rat. These results suggest dissimilar efficiencies of the probes to recover antipyrine, which should be uniformly distributed throughout body water. Dialysates from blood, brain, and liver probes in rats that received both antipyrine and tritiated water (3H2O) showed differences in antipyrine and 3H2O concentrations among probes. Variability of antipyrine and 3H2O concentrations over time within a probe were positively correlated, suggesting that the cause(s) of temporal variability affected both of these markers of body water. Correction of antipyrine tissue/blood ratios, using 3H2O blood/tissue ratios from the same sampling period, reduced the variability in antipyrine tissue/blood ratios, producing ratios closer to the expected value of 1. Differences in probe efficiency contributing to the variability of antipyrine and 3H2O recovery would also be expected to influence the recovery of other substances during microdialysis. The administration of antipyrine during microdialysis experiments is suggested to enable reduction of temporal and site-related differences in substance recovery that are due to differences in probe efficiency. Other methods are necessary to determine the actual extracellular concentration of dialyzed substances and the integrity of the blood-brain barrier.

Animals↗