Effect of moderate haemodilution with Fluosol-DA or normal saline on low-dose phenytoin and (+/-)-5-(4-hydroxyphenyl)-5-phenylhydantoin kinetics.
Phenytoin kinetics were determined in the rat following moderate (50%) blood exchange with either Fluosol-DA or normal saline. Rats received an intravenous phenytoin dose (10 mg kg-1) 0.5, 24, 48, or 72 h after exchange and were compared with non-exchanged controls. Phenytoin t 1/2 was not altered by exchange with either fluid. Its Cl and Vd were decreased and AUC increased 24, 48, and 72 h after saline exchange and 24 h after Fluosol-DA exchange. (+/-)-5-(4-Hydroxyphenyl)-5-phenylhydantoin (HPPH), a major metabolite of phenytoin, showed a decreased t1/2 and VHPPH 24, 48, and 72 h after exchange with either fluid; t1/2 was also reduced 0.5 h after Fluosol-DA exchange. The decreased Vd and VHPPH may result from changes in cardiac output secondary to haemodilution, or may represent a redistribution in the microcirculation. Fluosol-DA appears to enhance phenytoin and HPPH metabolism 48 and 72 h after exchange.
D000818:Animals; D004338:Drug Combinations; D005466:Fluorocarbons; D006400:Hematocrit; D006438:Hemodilution; D006895:Hydroxyethyl Starch Derivatives; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D010672:Phenytoin / Q000031:analogs & derivatives* / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains
D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; C027364:5-(3-hydroxyphenyl)-5-phenylhydantoin; D010672:Phenytoin; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination