Clearance studies of methotrexate in dogs after multiple-rate infusion.

Abstract

Plasma, renal, and nonrenal clearances of methotrexate as well as their interrelationship were studied in five conditioned male beagle-mongrel dogs using the multiple-rate infusion method. Steady-state plasma methotrexate concentrations of 1, 20, and 100 micrograms/ml were targeted for by i.v. bolus doses followed by i.v. infusions. An isotonic solution of sodium bicarbonate or ammonium chloride was simultaneously infused to study the effect of acid-base imbalance on the clearances. NaCl solution (0.9%) infusion served as a control. Plasma and urine concentrations of methotrexate were quantitated by a sensitive high-performance liquid chromatographic method. Distortion of body acid-base balance did not significantly change the clearances of methotrexate. The results showed that the plasma clearance (4.02 to 4.68 ml/min/kg) of methotrexate was relatively constant over the concentration range studied. The renal and nonrenal clearances, on the other hand, were concentration dependent. As the plasma methotrexate concentration increased from 1 to 20 or 100 micrograms/ml, renal clearance decreased from 3.60 to 4.28 ml/min/kg to 2.62 to 2.73 ml/min/kg, and nonrenal clearance increased form 0.35 to 0.42 ml/min/kg to 1.38 to 1.74 ml/min/kg. Concentration-dependent renal clearance may be due to saturation of the process involving active tubular secretion of methotrexate.

• Authors: C Y Lui, M G Lee, W L Chiou
• Journal: Cancer research (Cancer Res) Vol. 45 Issue 4 Pg. 1545-8 (Apr 1985) ISSN: 0008-5472 [Print] United States
• PMID: 3978622 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Methotrexate

Topics

• Animals
• Dogs
• Hydrogen-Ion Concentration
• Infusions, Parenteral
• Kidney (metabolism)
• Male
• Metabolic Clearance Rate
• Methotrexate (administration & dosage, metabolism)