title: Cephalosporin clinical concentration-time profile modelling and in-vitro bactericidal effects on Escherichia coli.
abstract: We assessed the cephalosporin concentration-time curve area (AUC), peak concentration, maintained concentration and duration of exposure on in-vitro bactericidal effects on Escherichia coli NCTC 10418, using exposures modelling cephazolin clinical profiles after 1 g and 2 g i.m. injection, equal AUC exposures (288 mg x h/L, 576 mg x h/L; 48 h) and constant exposures to 6, 12 and 24 mg/L. Cephalosporin dosage exposures based on maintenance of concentrations at multiples (6-24 times) of the MIC were not as effective in early or sustained (24 h) bactericidal effect as exposures modelling im injection profiles with equal or lower AUC (P<0.05, ANOVA). Similar results applied to i.m. comparisons with equal AUC exposures modelling extremes of concentration and time exposures. These results indicate a need for intermittent dosage to produce optimally effective profiles, and raise the possibility that these optimum dosing profiles may allow an extension of minimum interdose intervals beyond 8 h.
authors.affiliation: Department of Clinical Pharmacology, Alfred Hospital, Prahran, Australia.
authors.forename: K A
authors.initials: KA
authors.lastname: Cholewka
authors.forename: L L
authors.initials: LL
authors.lastname: Ioannides-Demos
authors.forename: L
authors.initials: L
authors.lastname: Liolios
authors.forename: P
authors.initials: P
authors.lastname: Paull
authors.forename: W J
authors.initials: WJ
authors.lastname: Spicer
authors.forename: A J
authors.initials: AJ
authors.lastname: McLean
mesh_terms: D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008954:Models, Biological
chemical_list: D002511:Cephalosporins