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I was wondering if anybody can help me with an eye PK study.
We're about to embark on a study to investigate penetration of
Linezolid into the non-inflamed human eye. The aim of this study is
to determine whether sufficient MIC90 are achieved.
MIC90 values of linezolid for susceptible organisms lie in the range
1-4mg/L. Linezolid produces peak serum levels of 18mg/L after
repeated oral doses of 625mg. In animal studies linezolid reaches
concentrations in the eye which are 40% of serum levels.
We aim to measure linezolid levels in patients undergoing elective
opthalmic procedures. 30 patients are to be given a single dose of
600mg linezolid tablet at a designated time prior to surgery. As
soon as convenient during surgery a sample of aqueous humour
(100microlitres) is to be collected. At the same time a sample of
blood will be taken. Only one aqueous humour sample, and one blood
sample will be taken.
My question to you is, in order to determine peak concentrations
achieved in the eye, and time to peak concentrations in the eye, how
would you arrange the sampling of aqueous humour/blood in the 30
patients?Would it be possible from the limited sampling to estimate
clearance from the eye?
Any help much appreciated.
Department of Pharmacy
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The pharmacodynamically-linked variable for linezolid is probably
Time > MIC according to Bill Craig's animal data. Therefore,
obtaining a single time point that is a near peak is relatively
I would suggest examining a paper our group put into the literature
regarding penetration of a fluoroquinolone (levofloxacin) into a body
site (the prostate) in patients undergoing prostatectomy. The
reference is Antimicrob Agents Chemother 2000;44:2046-2051.
In this study, patients all had the same plasma samples drawn, with
the acquisition times calculated by stochastic optimal design theory.
The patients were randomized to different drug dosing times, so that
the scheduled prostatectomy occurred at different times after drug
administration. All the plasma and tissue data were then co-modeled
using a non-parametric population modeling approach (then NPEM, now
NPAG by Jelliffe, Schumitzky and Leary). Monte Carlo simulation was
then employed to examine the extent of tissue peentration and its
variability in the population.
Hope this helps.
All the best.
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