[Pharmacokinetics of propranolol, phenytoin and lidocaine in hypercholesterolemic rabbits]

1. The aim of this study was to investigate an eventual influence of hypercholesterolemia on drug kinetics in the rabbit. Pharmacokinetic of propranolol, phenytoin and lidocain was studied in groups of male "Fauve de Bourgogne" rabbits. Each compound was administered by intravenous single dose injection, dosage being 1 mg/kg for propranolol, 10 mg/kg for phenytoin, and 3,5 mg/kg for lidocain. Propranolol plasma levels were determined by spectrofluorimetric method; plasma concentrations of phenytoin and lidocain were determinated according to a gas chromatographic method. 2. Our data showed variations of pharmacokinetic parameters for propranolol and phenytoin only. For propranolol the total body clearance (0,178 +/- 0,064 and 0,115 +/- 0,048 l.kg-1.mn-1; p less than 0,05) and the volume of distribution (9,32 +/- 3,10 and 6,02 +/- 0,96 l.kg-1; p less than 0,01) were significantly diminished; half-life (40,25 +/- 19,45 and 45,62 +/- 32,20 mn) remained inchanged. For phenytoin, total body clearance (3,28 +/- 0,94 and 1,43 +/- 0,50 l.kg-1.mn-1; p less than 0,001) was significantly diminished; half-life (136,4 +/- 29,4 and 324,9 +/- 131,6 mn; p less than 0,001) significantly increased; volume of distribution (0,62 +/- 0,13 and 0,62 +/- 0,10 l.kg-1) remained unchanged. 3. These variations may be related to changes in the plasma binding for propranolol and in the hepatic metabolism for propranolol and phenytoin.