| Title |
Alteration of postantibiotic effect during one dosing interval of tobramycin, simulated in an in vitro pharmacokinetic model |
| Published in |
Antimicrobial Agents and Chemotherapy. ISSN 0066-4804. |
| Author |
Hollander, den J.G. (Jan); Mouton, J.W. (Johan); Goor, van M.P.J.; Vleggaar, F.P. (Frank); Verbrugh, H.A. (Henri) |
| Date |
1996-01-01 |
| Language |
English |
| Type |
article |
| Abstract |
The kinetics of the postantibiotic effect (PAE) during one dosing interval
of tobramycin against Staphylococcus aureus and Pseudomonas aeruginosa was
investigated. We determined the PAE at different time points during this
dosing interval of 12 h in an in vitro pharmacokinetic model simulating
human pharmacokinetics in which the half-life of tobramycin was adjusted
to 2.4 +/- 0.2 h. Using an enzymatic method to inactivate tobramycin, we
determined PAEs in samples extracted from the model at 1, 5, 8, and 12 h,
corresponding with tobramycin concentrations of 20, 5, 2, and 1 times the
MIC for the test organism. The PAE decreased significantly from 2.5 h at 1
h to 0 h at 12 h. No change in MIC was observed for the strains during the
experiments. We conclude that the PAE decreases with decreasing tobramycin
concentrations during a 12-h dosing interval and completely disappears
after the concentration has reached the MIC for the test organism. On the
basis of these observations, the emphasis that is placed on the PAE in
discussions about the optimal dosing interval in aminoglycoside therapy is
questionable. |
| Publication |
http://hdl.handle.net/1765/8627 |
| Persistent Identifier |
urn:NBN:nl:ui:15-1765/8627 |
| Metadata |
XML |
| Repository |
Erasmus University Rotterdam |