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Hello everybody,
Just a simple question,
Have anyone experience with drugs that act as inductors or inhibitors
of transport or metabolism systems after only one dose?
I will clarify my question.
In a single dose escalation study, I use the same animal. Could the
first (higher) dose modify PK parameters of the second (lower) dose?
or I should assume that the differences are related to nonlinearity or
residual variability?
And the time between doses is a major factor for results?
Thank you in advance.
Mark
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The following message was posted to: PharmPK
Mark,
If a drug is a suicide inhibiter then inhibition will last until the
amonut of enzyme can be replaced.
If the drug has a PD effect on the GI tract (eg proton pump inhibitor)
then you could get differences in PK and you need to wait for the PD
respnse to washout.
Susan
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Hi Mark,
The antimalarial drug artemisinin is capable of inducing enzyme
(including those responsible for its own metabolism) after a single
dose. Please see:
Ashton et al., Biopharm Drug Dispos. 1998 May;19(4):245-50
Gordi et al., Br J Clin Pharmacol. 2005 Feb;59(2):189-98
Toufigh Gordi
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Mark,
we have recently shown this with gemcitabine.
Journal of Clinical Oncology VOLUME 25 NUMBER 36 DECEMBER 20
2007:5704-5709.
Randomized Crossover Study Evaluating the Effect of Gemcitabine
Infusion Dose Rate: Evidence of Auto-Induction of Gemcitabine
Accumulation.
Regards
Peter
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