Characterization of maximal intravenous dose volumes in the dog (Canis familiaris).
1. Pharmacological evaluation of intravenously administered drugs is frequently limited by the dose volume. Commonly used osmolytes in dosing solutions are isotonic sodium chloride (0.9%) and dextrose (5%). 2. The objective of this study was to determine the maximum volume of an isotonic intravenous (i.v.) solution to be given to conscious dogs. 3. Four dogs (2 male, 2 female), prepared for urine collections and for blood pressure and heart rate determinations, were given saline or dextrose intravenously at infusion rates of 0.3 ml(kg min)-1, 1.0 ml(kg min)-1 or 3.0 ml(kg min)-1 for 60 min; a sham-infusion was also performed. 4. Hematocrit and serum osmolality, BUN, sodium, potassium, chloride, creatinine and glucose, urinary excretion of sodium, potassium, chloride, and urine flow rate, urine osmolality, and renal creatinine and glucose clearances were determined. 5. Intravenous infusion of greater than 1.0 ml(kg min)-1 (60 ml/kg) 0.9% saline was associated with significant hemodilution and tachycardia. 6. Intravenous infusion of greater than 0.3 ml(kg min)-1 (18 ml/kg) 5% dextrose was associated with significant hemodilution, hyponatremia, tachycardia and delayed CNS disturbances associated with hyponatremia. 7. Hence, the limiting volumes of isotonic vehicles that can be administered intravenously to conscious dogs without contributing substantial effects on systemic or renal function are approx. 60 ml/kg 0.9% saline (or an equivalent non-metabolizable osmolyte) and approx. 18 ml/kg 5.0% dextrose (or an equivalent metabolizable osmolyte), administered over 60 min.
Mann
W A
WA
Department of Toxicology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Kinter
L B
LB
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004285:Dogs; D005260:Female; D005947:Glucose / Q000008:administration & dosage*; D006339:Heart Rate; D006400:Hematocrit; D007262:Infusions, Intravenous; D007552:Isotonic Solutions; D007668:Kidney / Q000502:physiology; D008297:Male; D009994:Osmolar Concentration; D012965:Sodium Chloride / Q000008:administration & dosage*; D014554:Urination
D001786:Blood Glucose; D007552:Isotonic Solutions; D012965:Sodium Chloride; D005947:Glucose