Biotransformation kinetic of binifibrate and identification of its metabolites.
The metabolism of binifibrate was studied in 10,000 g supernatant fractions from rat liver. Binifibrate was found to be completely biotransformed into clofibric acid and nicotinic acid at 60 min from the start of incubation through a series of intermediate products among which glycerol dinicotinate was identified. The biotransformation constant of binifibrate into its different metabolites proved to be 0.11 +/- 0.025 min-1. The formation of clofibric acid follows a first-order kinetic process characterized by its corresponding rate constant (kc), proving to be 0.043 +/- 0.017 min-1. The amount of clofibrate was 0.78 +/- 0.16 mumol/ml, showing that it is not biotransformed later in the incubation mixture. The formation constant of nicotinic acid (kn) was 0.067 +/- 0.020 min-1 and the amount of substance contained in the incubation mixture (0.94 +/- 0.25 mumol/ml shows that it is later biotransformed in the incubation mixture through the previously described metabolic processes.
Sánchez-Torres
J M
JM
Department of Pharmacy, Faculty of Pharmacy, University of Salamanca, Spain.
Pedraz
J L
JL
Gascón
A R
AR
Begoña Calvo
M
M
Hernández
R M
RM
Domínguez-Gil
A
A
D000818:Animals; D001711:Biotransformation; D002995:Clofibric Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D009525:Niacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D009539:Nicotinic Acids / Q000493:pharmacokinetics*; D011355:Prodrugs; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
D009539:Nicotinic Acids; D011355:Prodrugs; D009525:Niacin; D002995:Clofibric Acid; C038877:binifibrate