Cephalosporin clinical concentration-time profile modelling and in-vitro bactericidal effects on Escherichia coli.
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.
Cholewka
K A
KA
Department of Clinical Pharmacology, Alfred Hospital, Prahran, Australia.
Ioannides-Demos
L L
LL
Liolios
L
L
Paull
P
P
Spicer
W J
WJ
McLean
A J
AJ
D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008954:Models, Biological
D002511:Cephalosporins