The effect of varying percentages of haemodilution with fluosol-DA or normal saline on antipyrine metabolism in the rat.
Antipyrine disposition and metabolism in conscious, unrestrained rats after 25 or 50% haemodilution with Fluosol or normal (0.9% NaCl) saline is reported. Rats received an intravenous antipyrine dose (20 mg kg-1) 0.5, 24, 48, or 72 h after haemodilution and its pharmacokinetic parameters have been compared with non-exchanged control animals. Haemodilution 25% with Fluosol initially depressed antipyrine metabolism for 24 h by decreasing the antipyrine urinary excretion rate constant and the formation rate constants of 4-hydroxyantipyrine (4-OH) and 3-hydroxymethylantipyrine (3-OHME). Metabolism was then increased for 48 and 72 h with a slight increase in all rate constants. Haemodilution 50% with Fluosol produced a similar pattern but with significant increases in the 3-OHME formation rate constant found at 48 and 72 h. Haemodilution 25% with saline reduced 4-OH formation for 48 h. Haemodilution 50% with saline significantly reduced antipyrine urinary excretion at all times. After a significant increase in the 4-OH and 3-OHME formation rate constants at 24 h following 50% haemodilution with saline, the rate constants were significantly decreased at 48 and 72 h. Haemodilution 25% with Flusol significantly reduced the antipyrine Vd at 0.5 and 72 h. After haemodilution 50% with Fluosol, the Vd alternated between values greater and less than control throughout the 72 h. Haemodilution 25 or 50% with saline had little influence on Vd.
D000818:Animals; D000983:Antipyrine / Q000378:metabolism* / Q000493:pharmacokinetics; D004338:Drug Combinations / Q000494:pharmacology; D005466:Fluorocarbons / Q000494:pharmacology*; D006400:Hematocrit; D006438:Hemodilution; D006895:Hydroxyethyl Starch Derivatives; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology
D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D012965:Sodium Chloride; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; D000983:Antipyrine