The effect of varying extents of Fluosol-DA or normal saline haemodilution on the dose dependent kinetics of phenytoin in the rat.
Phenytoin kinetics were determined in rats in which the blood was moderately haemodiluted with 20 or 40 mL kg-1 of Fluosol-DA or normal saline. Rats received one of three intravenous phenytoin doses (10, 40, 50 mg kg-1) 0.5, 24, 48, or 72 h after haemodilution and were compared with non-exchanged controls. Haemodilution with either 20 or 40 mL kg-1 of Fluosol or saline had no influence on the dose-dependent kinetics of phenytoin. Haemodilution with 40 mL kg-1 of Fluosol decreased the half-life of phenytoin's major metabolite, HPPH, after a 50 mg kg-1 dose. Neither Fluosol nor saline haemodilution affected the normal delay in biliary cycling of HPPH.
Shrewsbury
R P
RP
Division of Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
Oliver
S R
SR
Lewis
L M
LM
Anderson
W T
WT
White
L G
LG
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations / Q000494:pharmacology; D005466:Fluorocarbons / Q000494:pharmacology*; D006207:Half-Life; D006438:Hemodilution; D006895:Hydroxyethyl Starch Derivatives; D010672:Phenytoin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats
D001802:Blood Substitutes; D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; C001419:hydroxyphenytoin; D010672:Phenytoin; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination