Determination of extracellular methotrexate tissue levels by microdialysis in a rat model

Cancer Chemotherapy and Pharmacology
P O EkstrømL Slørdal

Abstract

We used a microdialysis technique to determine tissue methotrexate (MTX) levels during steady state in a rodent model. Two different approaches were employed to measure the actual extracellular MTX concentrations in muscle, liver, and kidney tissues of anesthetized Wistar rats. With the reduced-perfusion-rate technique, the flow in the microdialysis perfusate was gradually decreased toward zero to permit calculation of zero-flow intercepts. Using the net change technique, microdialysis probes were perfused with different MTX concentrations to allow an assessment of equilibrium drug levels. For these two methods to be used, drug concentrations in the matrix to be analyzed must remain unchanged during the experimental procedure. In the animal model, steady state was attained after 1.5 h and maintained throughout the rest of the experiments by the administration of MTX as continuous infusions through a venous catheter. In vitro and in vivo, both the reduced-perfusion-rate and net change techniques gave reproducible data that permitted the estimation of extracellular drug concentrations in the dialyzed tissue compartments.The data suggest that the level of unbound MTX in the circulation is fairly similar to the extracellular concen...Continue Reading

References

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Jan 1, 1995·Cancer Chemotherapy and Pharmacology·P O EkstrømL Slørdal
Jan 1, 1994·Cancer Chemotherapy and Pharmacology·O EkstrømL Slørdal

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Citations

Sep 28, 1998·Cancer Chemotherapy and Pharmacology·M J Egorin
Apr 28, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Nele Plock, Charlotte Kloft
Dec 8, 2000·Advanced Drug Delivery Reviews·A de la PeñaH Derendorf
Jan 6, 1999·Journal of Pharmaceutical Sciences·D K HansenC E Lunte

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