In vitro simulated pharmacokinetics profiles: forecasting antibiotic optimal dosage.
Sisomicin (SMN) and cefotaxime (CTX) antimicrobial effect (AME) kinetics were studied under in vitro stimulation the drug monoexponential pharmacokinetic profiles mimicking normal and impaired elimination of SMN or CTX administered in various doses to humans. Similar general shape of the AME intensity or duration vs the SMN and CTX AUC curves, i.e. the appearance of the "bacteriostatic" and "bactericidal" phases, was established irrespective of the antibiotic elimination rate. At the same time the AME vs AUC curves simulated normal and delayed drug elimination did not match. Thus, AME is defined not only the AUC value but also the peculiarities of the pharmacokinetic profile and, subsequently, the term of "antibiotic efficient concentration" is unseparable of the pharmacokinetic profile.
Firsov
A A
AA
National Research Institute of Antibiotics, Moscow, USSR.
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D002439:Cefotaxime / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000378:metabolism; D008954:Models, Biological; D012853:Sisomicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002439:Cefotaxime; D012853:Sisomicin