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Influence of C6 and CNS1 brain tumors on
methotrexate pharmacokinetics in plasma and brain tissue
Sylvain F. Dukic, Matthieu L. Kaltenbach, Tony Heurtaux, Guillaume Hoizey, Aude
Lallemand and Richard Vistelle
Laboratoire de
Pharmacologie et de Pharmacocinétique, U.F.R. de Pharmacie, Université de
Reims Champagne Ardenne (S.F.D., M.L.K., T.H.,
R,V.); Laboratoire de Pharmacologie et de
Toxicologie (G.H.), Laboratoire Pol Bouin (A.L.), Service
d’Histologie et de Cytologie, Hôpital Maison-Blanche, CHRU de Reims, Reims,
France. sylvain.dukic@univ-reims.fr
Purpose. Comparison of the influence of two different brain tumors (C6
and CNS1 glioma) on methotrexate (MTX) disposition in plasma, brain, and tumor
tissue extracellular fluid (ECF).
Methods. Serial collection of plasma samples and brain ECF dialysates
after i.v. bolus administration of MTX (50 mg kg(-1)) for 4 h.
Quantitation of MTX concentrations by HPLC-UV.
Results. Histological studies revealed a 3-fold higher number of blood
vessels in CNS1 than in C6 tumor tissue.
In vivo recoveries (reverse dialysis) were significantly different in tumor
tissue (C6: 8.0 +/- 3.8%; CNS1: 4.9 +/- 2.5%), and in the contralateral
hemisphere (C6: 6.0 +/- 4.0%; CNS1: 3.9 +/- 2.5%) between the two tumors.
Area under the concentration-time curve (AUC) in plasma was 30% higher in CNS1
than in C6 due to a lower systemic clearance.
Maximum MTX levels in brain tumor ECF were significantly higher in CNS1 than in
C6, and decreased faster in CNS1 than in C6 tumor-bearing rats.
Penetration in tumor ECF (AUC(ECF)/AUC(Plasma) ratio) was similar in CNS1 and
C6.
MTX concentrations in contralateral hemisphere were significantly lower than in
tumor tissue and dependent on tumor model.
Conclusion. C6 and CNS1 brain tumors have a distinct yet highly
variable impact on MTX penetration in brain and brain tumor ECF.
PMID: 15072460 [PubMed]
Soutce: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15072460
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