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  • 1
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    Brain tissue characterisation by infrared imaging in a rat glioma model (2006)
    Elsevier
    Details
    Publication Date: 2006-07-01
    Print ISSN: 0005-2736
    Electronic ISSN: 1879-2642
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Published by Elsevier
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    PAPER CURRENT
  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of Methotrexate in the Extracellular Fluid of Brain C6-Glioma After Intravenous Infusion in Rats (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1219-1225 
    Details
    ISSN: 1573-904X
    Keywords: C6-glioma ; methotrexate ; microdialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Establishment of the pharmacokinetic profile of methotrexate (MTX) in the extracellular fluid (ECF) of a brain C6-glioma in rats. Methods. Serial collection of plasma samples and ECF dialysates after i.v. infusion of MTX (50 or 100 mg/kg) for 4 h. HPLC assay. Results. Histological studies revealed the presence of inflammation, edema, necrosis, and hemorrhage in most animals. In vivo recovery (reverse dialysis) was 10.8 ± 5.3%. MTX concentrations in tumor ECF represented about 1−2% of the plasma concentrations. Rapid equilibration between MTX levels in brain tumor ECF and plasma. ECF concentrations almost reached steady-state by the end of the infusion (4 h), then decayed in parallel with those in plasma. Doubling of the dose did not modify MTX pharmacokinetic parameters (t1/2α, t1/2β, MRT, fb, Vd, and CLT), except for a 1.7-fold increase of AUCPlasma and a 3.8-fold increase in AUCECF which resulted in a 2.3-fold increase in penetration (AUCECF/AUCPlasma). In spite of an important interindividual variability, a relationship between MTX concentrations in plasma and tumor ECF could be established from mean pharmacokinetic parameters. Conclusions. High plasma concentrations promote the penetration of MTX into brain tissue. However, free MTX concentrations in tumor ECF remain difficult to predict consistently.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018945529611
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  • 3
    Electronic Resource
    Electronic Resource
    Determination of Free Extracellular Levels of Methotrexate by Microdialysis in Muscle and Solid Tumor of the Rabbit (1998)
    Springer
    Pharmaceutical research 15 (1998), S. 133-138 
    Details
    ISSN: 1573-904X
    Keywords: microdialysis ; methotrexate ; muscle ; VX2 carcinoma ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine of the pharmacokinetic profile of methotrexate (MTX) in blood and extracellular fluid (ECF) of VX2 tumor and muscle in rabbits. Methods. Microdialysis probes were inserted into VX2 tumor and in muscle tissue. Following intravenous administration of MTX (30 mg/ kg), serial collection of arterial blood samples and dialysates of muscle and tumor ECF for 4 h was carried out. Quantitation of MTX and determination of free plasma concentrations was performed by fluorescence polarization immunoassay and ultrafiltration, respectively. Correlations were established between the unbound plasma and ECF MTX concentrations. Results. Total and free plasma concentrations exhibited a parallel three exponential decay in both healthy and tumorigenic animals. Total clearance (8.9 vs 6.5 ml−1.min−1.kg−1) and volume of distribution (4.0 vs 2.9 1.kg−1), however, tended to decrease in the tumor-bearing group. The ECF/plasma AUC ratio equaled 14.2 ± 8.8% in muscle and 23.9 ± 15.9% in tumor. The concentration-time profile of muscle ECF MTX was parallel and highly correlated (r = 0.97) to that determined in plasma. In contrast, free MTX plasma levels were not correlated with tumor ECF concentrations (r = 0.564). Conclusions. In addition to the well-known pharmacological variability in the concentration-effect relationship, the important inter-individual variability in tumor exposure to MTX may partly explain that studies in patients with solid tumors have often failed to demonstrate firm correlations between MTX blood pharmacokinetics and the chemotherapeutic response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011973409022
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  • 4
    Electronic Resource
    Electronic Resource
    Distribution of Gacyclidine Enantiomers in Spinal Cord Extracellular Fluid (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 148-153 
    Details
    ISSN: 1573-904X
    Keywords: enantiomers ; extracellular fluid ; gacyclidine ; micro-dialysis ; spinal cord
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Determination of the pharmacokinetics of gacyclidineenantiomers, a non-competitive NMDA antagonist, in plasma and spinal cordextracellular fluid (ECF) of rats. Methods. Implantation of microdialysis probes in spinal cord (T9).Serial collection of plasma samples and ECF dialysates over 5 hoursafter IV bolus administration of (±)-gacyclidine (2.5 mg/kg). Plasmaprotein binding determined in vivo by equilibrium dialysis. ChiralGC/MS assay. Results. Plasma concentrations of (+)-gacyclidine were ∼25% higherthan those of (−)-gacyclidine over the duration of the experiment inall animals. Plasma concentrations decayed in parallel in a biphasicmanner (t1/2α ∼9 min; t1/2β ∼90 min) with no significant differencebetween enantiomers. Clearance and volume of distribution of(−)-gacyclidine were approximately 20% higher than those of its opticalantipode (CL: 248 vs 197 ml.kg−1.min−1;Vdβ: 31.6 vs 23.5 l/kg).Protein binding (∼90%) was not stereoselective. Both gacyclidineenantiomers were quantifiable in spinal cord ECF 10 min after drugadministration and remained stable over the duration of the experimentin spite of changing blood concentrations. Penetration of(−)-gacyclidine was significantly higher (∼40%) than that of (+)-gacyclidine inall animals. Yet, exposure of spinal cord ECF was similar for bothenantiomers, and not correlated with plasma AUCs. Conclusions. The disposition of gacyclidine enantiomers isstereoselective. Both enantiomers exhibit a high affinity for spinal cord tissueand their distribution may involve a stereoselective and active transportsystem. This hypothesis could also explain the discrepancy betweendrug concentrations in plasma and spinal cord ECF.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007557028313
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  • 5
    Electronic Resource
    Electronic Resource
    A Redox-Based System that Enhances Delivery of Estradiol to the Brain: Pharmacokinetic Evaluation in the Dog (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 879-883 
    Details
    ISSN: 1573-904X
    Keywords: estradiol ; chemical delivery system ; brain enhanced drug delivery ; blood–brain barrier ; pharmacokinetics ; redox drug delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of a dihydropyridine–pyridinium salt-type chemical delivery system (CDS) for brain-targeted delivery of estradiol (E2) were examined in dogs. Parameters evaluated in vitro included stability in buffers and biological fluids and plasma protein binding. In vivo studies examined drug and metabolite concentrations in plasma, urine, and cerebrospinal fluid as well as in selected brain regions. The administered lipophilic E2-CDS disappeared very quickly from plasma and was not detected in urine. The oxidized drug form, E2-Q+, was excreted unchanged or as a conjugate in the urine for as long as 2 weeks. Plasma levels were below assay detection limits at later times. Pharmacokinetic analysis of urine E2-Q+ levels allowed estimation of a half-life of 2.2 days. Amounts of E2-Q+ excreted into the urine were proportional to the dose but averaged only 13.9% of the dose, indicating that other routes of excretion must be considered. CSF levels were below the limit of detection for both E2-CDS and E2-Q+, however, brain tissue concentrations of E2-Q+ were similar in several brain regions of individual animals examined 1 or 3 days after drug dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015977319212
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