Pharmacokinetic profile of dodecanedioic acid, a proposed alternative fuel substrate.
Dodecanedioic acid (C12), a saturated, aliphatic dicarboxylic acid with 12 carbon atoms, was given as an intravenous bolus (800 mumol/kg of body weight [kgBW]) in male Wistar rats to study its pharmacokinetic profile. Because total plasma C12, which results from the sum of both free and albumin binding fractions, was measured by high-performance liquid chromatography, an in vitro experimental session was carried out to determine the binding curve of C12 in rat plasma. These data were then used to calculate the plasma C12 free fraction in in vivo experiments. The best fit obtained for the experimental data of albumin binding was obtained with the equation of reversible, saturable binding to one, two, or three classes of noninteracting equivalent sites. Only a single binding site was clearly identified with a dissociation constant of 147 mumol/L and a maximal predicted binding of 1.57 mol/mol albumin. The urinary excretion of C12 was 3.90 +/- 1.62% of the administered dose. The pharmacokinetic analysis was performed by one-compartment model with linear transfer to the tissues, taking into account simultaneously both plasma concentration and urine excretion data. The apparent volume of distribution of C12 was 0.248 +/- 0.035 L/kgBW, the apparent first order rate constant to the tissues was 0.0535 +/- 0.0123 min-1 and that from plasma to urine was 0.00206 +/- 0.00051 min-1. The C12 plasma half-life was 12.47 minutes. Renal clearance was 0.00051 L/kgBW per minute, whereas the systemic clearance was 0.0138 L/kgBW per minute. Because the renal clearance was much less than the rat inulin clearance reported in literature, the presence of C12 passive back-diffusion was hypothesized.
Mingrone
G
G
Istituto di Clinica Medica, Università Cattolica S. Cuore, Roma, Italy.
Greco
A V
AV
De Gaetano
A
A
Tataranni
A
A
Raguso
C
C
Castagneto
M
M
D000818:Animals; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D003998:Dicarboxylic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006207:Half-Life; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism
D003998:Dicarboxylic Acids; D012709:Serum Albumin; C036836:dodecanedioic acid