[Pharmacokinetic basis of the nephrotoxic action of sisomycin. The pharmacokinetics of sisomycin in single and multiple administrations to rats].
The pharmacokinetics of sisomicin was studied on Wistar rats. The antibiotic was used in single or repeated doses of 12.5 and 25 mg/kg. The kinetic data of the antibiotic titration in blood serum within 1 and 24 hours of intramuscular administration of the drug were formalized with the use of a linear two-compartment model. The average values of the elimination constant and the constants of sisomycin transfer from the central compartment into the peripheral one were 0.64, 0.34 and 0.13 hours-1 respectively. The value of the apparent distribution volume in the central compartment was 0.38 ml/kg and that of the stationary and kinetic distribution volumes was 1.37 and 3.06 1/kg respectively. The value of the general clearance was 0.24 1/(kg.hour) and that of the sisomicin half-life was 8.7 hours. Comparison of the antibiotic levels estimated with a model and actually measured in the blood after repeated administrations revealed the drug cumulation. When the antibiotic was used in a dose of 25 mg/kg daily, its cumulation was observed earlier (by the 5th--8th day) than on its use in a dose of 12.5 mg/kg (by the 30th day). Irrespective of the dose, sisomicin cumulation was accompanied by prolongation of the antibiotic half-life in the rats.
D000818:Animals; D005260:Female; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D008433:Mathematics; D051381:Rats; D012853:Sisomicin / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D013997:Time Factors
D005839:Gentamicins; D012853:Sisomicin
Farmakokineticheskoe obosnovanie nefrotoksicheskogo deĭstviia sizomitsina. Farmakokinetika sizomitsina pri ego odnokratnom i mnogokratnom vvedenii krysam.