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Dear all,
Is there any other reason for double peak phenomenon in i.v. pk profile
in rats other than enterohepatic cycling.
Thanks in advance
Regards
Neeraj
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Hello Neeraj,
In case the drug is lipophilic and gets intially sequestered in highly
perfused organs, a redistriution via slow release of drug from
theselocalpools can be a plausible explaination for double peaks in
IV PKstudy.
Good luck
vijay
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The following message was posted to: PharmPK
Hi Neeraj and Vijay:
Vijay suggests that if the drug is lipophilic it might
be getting initially sequesterd in organs and then
gets redistributed by slow release whichs leads to the
double peak, following IV dosing. If it is so
conc-time curve should should show a gradually rising
conc (as it gets slowly redistributed from the
organs), which will be different from a peak usually
observed at Tmax following an PO dosing.
Ananda
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We have seen the double peak scenario in patients receiving lipophilic
drugs. The catch is that with the slow re-distribution you have an
additive effect so that the expected peak is far below the calculated
peak for the given dose. This will normally follow a less than expected
peak with your first draw.
I have seen this occur clinically with severely ill children who are
third spacing secondary to sepsis. The drug in question may be
minimally lipophilic but gets carried out in the wash then re-appears
at the most inopportune time.
I am not sure that you can duplicate this in research but it is a
common phenomenon in clinical practice.
Patient specific details and drugs monitored if needed.
Thanks........... Robert
Robert Aucoin, RPh
Clinical Pharmacist - Peds
Department of Pharmacy Office: 225-765-7652
Our Lady of the Lake RMC Pager: 225-237-6564
5000 Hennessy Blvd Toll Free: 888-765-7428
Baton Rouge, La 70808
RAucoin.aaa.ololrmc.com
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