Non-linear tissue binding of amikacin in rats: the effect of renal impairment.
Amikacin levels in serum and tissues were determined in 115 Wistar rats, 70 with normal renal function (NRF) and the remaining 45 with terminal renal impairment (TRI). The results obtained in the animals with NRF show an accumulation of the antibiotic in all the tissues studied as compared with plasma levels, specially in the renal cortex and medulla. In the rats with TRI important alterations in the plasma and tissue kinetics of the antibiotics were observed. The plasma kinetics of amikacin in rats with TRI are characterised by significant alterations in the pharmacokinetic parameters, specially those defining the distribution processes of the antibiotic. In the tissues of the latter, a significant increase in the antibiotic concentration takes place, particularly in the renal cortex. The average half-lives of the antibiotic in the tissues of rats with TRI increase compared with the group of rats with NRF, though the difference are not so significant as in the case of the plasma half-life. The use of a specific kinetic distribution model, with linear and non-linear tissue binding, showed that significant variations occur in the partition coefficient and in the Michaelis-Menten parameters, which characterize the saturable binding of Amikacin to tissue in rats with NRF and TRI.
Department of Pharmacy, Faculty of Pharmacy, University of Salamanca, Spain.
I G
IG
Alonso
J M
JM
Lanao
M C
MC
Saez
A A
AA
Dominguez-Gil
A
A
Dominguez-Gil
D000583:Amikacin / Q000493:pharmacokinetics*; D000818:Animals; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000583:Amikacin