[Correlation of dose-antimicrobial effect in modeling in vitro pharmacokinetic profiles of normal and impaired elimination of antibiotics].
Relationships between concentration and antimicrobial effect (AME) of sisomicin (SMN) and cefotaxime (CTX) were established by simulating their pharmacokinetic profiles in an in vitro dynamic model. The AME duration (TE, time shift between the curves of bacteria heat output in the presence and absence of the antibiotics) or intensity (IE, area between the above curves) for both the antibiotics depended in the same way on the area under the concentration/time curve (AUC, mimicing of intravenous administration of the antibiotics in various doses). At low and moderate values of the AUC the dependences of IE or TE vs the AUC (the bacteriostatic phase of the AME development) were of the sigmoid shape while at high values of the AUC there was a marked increase in IE or TE (the bactericidal phase). The patterns of the IE or TE vs AUC curves in impaired antibiotic elimination were analogous. At the same time the IE or TE vs AUC curves for both the antibiotics under simulation of normal elimination (T 1/2, SMN-2.1 h, T 1/2, CTX-1.2 h) and impaired one (T 1/2, SMN-8.3 h, T 1/2, CTX-4.6 h) did not match. In the first case the AMESMN was on the whole higher and the AMECTX was lower than in the second case. Therefore, in patients with renal failure the efficient concentration of the aminoglycoside in blood can be higher and that of the cephalosporin on the contrary can be lower than the normal.
Firsov
A A
AA
D002439:Cefotaxime / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D066298:In Vitro Techniques; D008657:Metabolic Clearance Rate; D012853:Sisomicin / Q000008:administration & dosage* / Q000493:pharmacokinetics
D002439:Cefotaxime; D012853:Sisomicin
Sootnosheniia kontsentratsii/antimikrobnyĭ éffekt pri modelirovanii in vitro farmakokineticheskikh profileĭ normal'noĭ i narushennoĭ éliminatsii antibiotikov.