[Sisomycin pharmacokinetics in the perilymph and blood serum--an approach to predicting its ototoxic effect].
To elucidate the possibility of predicting the level of aminoglycoside antibiotic penetration into the fluids of the internal ear by the antibiotic blood levels, the pharmacokinetics of sisomicin in the perilymph and blood serum was studied on guinea pigs. The antibiotic was administered to the animals subcutaneously in doses of 50, 100 and 200 mg/kg. On the basis of the comparison of the sisomicin concentrations in the perilymph normalized against the dose it was concluded that the pharmacokinetics of sisomicin in the perilymph and blood serum of the animals was linear. Comparison of the areas under the curves of the antibiotic concentration versus time in the perilymph (AUCp) and blood serum (AUCs) showed that the tissue availability of the antibiotic in this study characterized by its penetration into the perilymph and defined by the ratio of the AUCp to AUCs amounted to 55 per cent. In a two-compartment model it was not possible to predict the antibiotic levels in the perilymph by concentrations in the blood. However, by the antibiotic blood levels it was possible to characterize in a complex the pharmacokinetic behaviour of the antibiotic in the perilymph by predicting the areas under the respective curves of the antibiotic concentration versus time. The proportional relation between the values of the AUCp and AUCs suggested that the level of the antibiotic penetration into the internal ear and consequently the intensity of the potential ototoxic effect could be more reliably predicted not by separate values of the antibiotic concentration but by the areas under curves of aminoglycoside concentrations versus time.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000187:drug effects*; D006168:Guinea Pigs; D007700:Kinetics; D007761:Labyrinthine Fluids / Q000378:metabolism*; D008954:Models, Biological; D010498:Perilymph / Q000378:metabolism*; D011379:Prognosis; D012853:Sisomicin / Q000378:metabolism* / Q000633:toxicity; D013997:Time Factors
D012853:Sisomicin
Izuchenie farmakokinetiki sizomitsina v perilimfe i syvorotke krovi--podkhod k prognozirovaniiu ototoksicheskogo éffekta.