Tolerable infusion rate of citrate based on clinical signs and the electrocardiogram in conscious dogs.
OBJECTIVE
The possible clinical significance of the toxic effects of citrate has not yet been fully clarified. This study was therefore conducted to confirm the toxicity and determine the tolerable infusion rate of citrate administered by rapid intravenous infusion to conscious dogs.


METHODS
Citrate solutions were infused via the cephalic vein of 4 conscious dogs at 0.33, 0.67, or 1.33mmol/kg/h up to 1.33mmol/kg. Clinical signs and the electrocardiogram were observed during and after infusion. Serum citrate and ionized calcium levels were also measured.


RESULTS
Although the mean citrate level increased in accordance with the infusion rate, the calcium level decreased. No significant changes in clinical signs or the electrocardiogram were observed during infusion at 0.33mmol/kg/h despite an increase in the serum citrate level to 1.22+/-0.11mmol/l (pre-infusion value: 0.38+/-0.01mmol/l) and a decrease in the serum calcium level to 1.28+/-0.03mmol/l (pre-infusion value: 1.50+/-0.05mmol/l). Vomiting and QTc prolongation were observed at 0.67mmol/kg/h or higher. Salivation and tachycardia were observed at 1.33mmol/kg/h.


CONCLUSIONS
Based on clinical signs and the electrocardiogram, the tolerable infusion rate of citrate in conscious dogs is concluded to be 0.33mmol/kg/h.
Fukuda
Tatsuru
T
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima 772-8601, Japan. fukudat2@otsukakj.co.jp
Toyoshima
Shigeki
S
Nakashima
Yoshifumi
Y
Koshitani
Osamu
O
Kawaguchi
Yoshiro
Y
Momii
Akira
A
D000818:Animals; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000633:toxicity; D019540:Area Under Curve; D002118:Calcium / Q000097:blood*; D019343:Citric Acid / Q000493:pharmacokinetics* / Q000633:toxicity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006996:Hypocalcemia / Q000139:chemically induced*; D007262:Infusions, Intravenous; D008133:Long QT Syndrome / Q000139:chemically induced; D008274:Magnesium / Q000097:blood; D008297:Male; D011897:Random Allocation; D012472:Salivation; D013610:Tachycardia / Q000139:chemically induced; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced
D000925:Anticoagulants; D019343:Citric Acid; D008274:Magnesium; D002118:Calcium