Further observations on the disposition characteristics of salicylic acid in analbuminemic rats.
The disposition characteristics of salicylic acid (SA) were investigated in analbuminemic rats after intravenous bolus injection of 10 and 173 mg kg-1 of SA to study the effects of plasma protein binding on drug disposition. Following the administration of 10 mg kg-1 of SA, total body SA clearance (CL) was markedly faster and its apparent volume of distribution (Vd) significantly greater in the analbuminemic rats in comparison to the controls. Further, the apparent elimination rate constant (kj) was two-fold greater and the corresponding elimination half-life (t 1/2) shorter in the rats with low plasma albumin. Whole body autoradiograms obtained following the administration of 14C-salicylic acid demonstrated that the tissue distribution of SA was greater in the analbuminemic rats which was in agreement with the larger Vd observed in this group of rats. After the administration of 173 mg kg-1 of SA, no differences in CL, Vd, kk or t 1/2 were noted between the analbuminemic and control rats. Dose-dependent SA disposition was observed in both the analbuminemic and control rats with the effects being more pronounced in the rats with low plasma albumin. The results suggested that the disposition characteristics of SA were markedly altered in the presence of low plasma albumin concentrations due to reduced plasma SA protein binding.
Hirate
J
J
Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University, Japan.
Kato
Y
Y
Horikoshi
I
I
Nagase
S
S
Ueda
C T
CT
D000818:Animals; D001345:Autoradiography; D001798:Blood Proteins / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012709:Serum Albumin / Q000172:deficiency*; D014018:Tissue Distribution
D001798:Blood Proteins; D012459:Salicylates; D012709:Serum Albumin