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What do PharmPK members think are the most appropriate PD targets (%
free
drug T>MIC) for cephalosporins, penicillins, and carbapenems versus
aerobic
Gram-negative bacteria, specifically when considering clinical outcome
as
the endpoint?
Thanks much for replies,
Craig A Wood, MD
National Scientific Director, Infectious Diseases
Merck & Co, Inc.
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The following message was posted to: PharmPK
Dear Dr. Wood,
I generally use a cutoff of 40%T>MIC (free drug levels sustained during
a dosing interval) as the PD target for cephalosporins, penicillins and
carbapenems. Correlations can then be made between attainment of this
PD target and clinical outcome and/or microbiologic response endpoints.
Kind Regards,
Leslie Floren, PharmD
Assoc. Dir. Pharmacology and Toxicology
Peninsula Pharmaceuticals, Inc.
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hi
In a nutshell: this depends on the drug, and there is some discussion
on this issue. the fT>MIC needed for carbapenems is around 30%, for
penicillins 40-50% and for cephalosporins 50-60% as can be concluded
from a number of animal experiments. In all cases, it is best to
indicate and state the motivation why a particular value was chosen,
e.g. a two log drop in animal experiments, or 80% of a maximum effect
(the values above are based on that). finally, when determining dosing
regimens, the variation in ppop pk has to be addressed for instance
using Monte Carlo Sims.
finally, the immune status of the patient groups and in particular the
indications of the drug should be taken into account as well.
johan mouton
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