Influence of high-dose methotrexate on the distribution of body fluid volumes in the dog.

We studied the influence of high-dose methotrexate (HDMTX) on body fluid volumes in the dog, using indicator dilution techniques. In six healthy mongrel dogs total body water volume (TBW), extracellular water volume (ECW), body mass, and plasma osmolality were measured before and after infusion of both saline and HDMTX. TBW and ECW were determined simultaneously, using a double-indicator (D2O/ferrocyanide), single injection technique. In vitro experiments confirmed the reliability of ferrocyanide as an indicator for ECW, also in the presence of methotrexate. Results showed an increase in ECW after HDMTX (P = 0.029, paired Student's t-test), while TBW remained constant. Infusion of the same volume of isotonic saline in the control experiments did not result in any demonstrable change in either TBW or ECW. Therefore, infusion of HDMTX appears to cause a water shift from the intracellular to the extracellular compartment. Such a change in body water volumes may have implications for estimates of body composition and for pharmacokinetic studies in cancer patients receiving HDMTX.