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The following message was posted to: PharmPK
Hi All,
I am conducting a pharmacokinetic study using midazolam (both oral and IV)
in a patient group and a group of age-, race-, and gender-matched healthy
control subjects. I am seeing a midazolam peak approximately four hours
after administration of IV midazolam (but not oral) in some patients from
both groups.
Does anyone have any information on whether or not midazolam undergoes
enterohepatic recirculation? I know diazepam does, but as I understand it,
midazolam is not thought to. I have searched the literature but found
nothing concrete.
Thanks,
Jennifer
--
Jennifer Bonner, PharmD
PhD Candidate
Department of Pharmaceutical Sciences
University of Pittsburgh School of Pharmacy
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The following message was posted to: PharmPK
Hello Jennifer,
I'm not sure what method you are using for analysis. If it is LC-MS, and the LC gradient is short, you may be confounded by in-source fragmentation of the direct N-glucuronide of midazolam. This metabolite could potentially appear at the later timepoint.
Originally reported by the Sanofi group:
Klieber et al. (2008) Drug Metab. Dispos. 36, 851-862.
and later recapitulated by Pfizer.
I'm not sure if this would fit your profile, but it seems much more likely than recirculation. If your subjects have been exposed to CYP3A inhibitors this would increase the role of the glucuronidation pathway.
All the very best,
Bernard
Bernard Murray, Ph.D.
Senior Research Scientist, Drug Metabolism
Gilead Sciences, Foster City CA
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