Abstract
We hypothesized that cytostatic agents per se, apart from the malignancy, may have an effect on body water distribution. The influence of high dose methotrexate (HDMTX) and doxorubicin on body fluid volumes in the dog was investigated. Firstly, total body water (TBW), extracellular water (ECW), body weight and plasma osmolality were measured in six healthy mongrel dogs with permanent catheters in aorta and pulmonary artery, before and after infusion of isotonic saline and HDMTX (dose=250 mg/kg in isotonic solution), respectively. TBW and ECW were determined simultaneously, using a double indicator (D2O/ferrocyanide), single injection technique. D2O was determined in red cells by an infrared spectrophotometric method; ferrocyanide (hexacyanoferrate II, Fe(CN)64∼) levels were spectrophotometrically assessed in plasma. One hour after HDMTX infusion we observed a increase in mean ECW from 225 to 244 ml/kg body weight (p=0.011, paired Student's t-test); this is an increase of 8.4 %. Mean TBW remained the same. The increase in ECW could not be explained by a simple volume effect as an equal volume of saline did not yield a significant change in extracellular fluid volume. Plasma osmolality decreased only 1% and therefore a simple osmotic mechanism was unlikely to have caused the observed fluid shift. No other drugs, known to influence water distribution, e.g. barbiturates, were administered. Results suggest a water shift across the cell membrane due to an effect of HDMTX. Similar experiments using doxorubicin (1 mg/kg) did not show any significant change in either TBW or ECW.
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De Graaf, S., De Vries, J., Zijlstra, W. et al. CYTOSTATIC AGENTS AND BODY FLUID VOLUMES IN THE HEALTHY DOG. Pediatr Res 19, 1122 (1985). https://doi.org/10.1203/00006450-198510000-00299
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DOI: https://doi.org/10.1203/00006450-198510000-00299