[Dependence of the antimicrobial effect on the antibiotic concentration in modelling pharmacokinetic profiles in vitro: a comparison of 2 regimens for the single intravenous administration of sisomicin]

Abstract

Kinetics of sisomicin antimicrobial effect on E. coli was studied in an in vitro dynamic model. Pharmacokinetic profiles observed in blood of humans treated with different polar dosing schedules i. e. bolus administration and continuous infusion were simulated. The first set of the experiments included simulating the profiles observed at short-term maintenance (0.25-20 min) of relatively high antibiotic levels after bolus administration (Cmax = 0.125-10 micrograms/ml). The second set included simulating the profiles observed at long-term maintenance (1-15 hours) of relatively low antibiotic levels after infusion (Cmax = 0.125-1.75 micrograms/ml). Changes in the viable count in the dynamic model were estimated microcolorimetrically with BioActivity Monitor LKB 2277-202. The use of the recently developed parameters of antimicrobial effect intensity IE and duration TE provided determination of relationship between IE or TE and logarithm of the area under the concentration-time curve (lg AUC). Its own IE (or TE) vs lg AUC curve including 4 phases corresponded to every administration schedule i. e. bolus and infusion. The 1st and 3rd phases reflected weak changes in IE or TE at significant increasing of the AUC and the 2nd and 4th phases reflected a marked increase in IE or TE at insignificant changing of the AUC.(ABSTRACT TRUNCATED AT 250 WORDS)