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Publication Detail
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Use of Accelerator Mass Spectrometry to Measure the Pharmacokinetics and Peripheral Blood Mononuclear Cell Concentrations of Zidovudine
Publish date: Jul 01, 2007
Author: Le T. Vuong, Jon L. Ruckle, Arlin B. Blood, Michael J. Reid, Richard D. Wasnich, Hans-Arno Synal, Stephen R. Dueker
Source: Journal Of Pharmaceutical Sciences
The remarkable sensitivity of accelerator mass spectrometry (AMS) is
finding many new applications in pharmacology. In this study AMS was used to
measure [14C]-Zidovudine (ZDV) concentrations at the drug's site of action (peripheral
blood mononuclear cells, PBMCs) following a dose of 520 ng (less than one-millionth of
the standard daily dose) to a healthy volunteer. In addition, the pharmacokinetics of
this microdose were determined and compared to previously published parameters for
therapeutic doses. Microdose ZDV pharmacokinetic parameters fell within reported 95%
confidence intervals or standard deviations of most previously published values for
therapeutic doses. Blood, urine, stool, saliva, and isolated PBMCs were collected
periodically through 96 h postdose and analyzed for ZDV and metabolite concentrations.
The results showed that ZDV is rapidly absorbed and eliminated, has one major
metabolite, and is sequestered in PBMCs. 14C mass balance assessments indicated a
significant portion of ZDV remained after 96 h with a much prolonged elimination half-
life. Results of this study demonstrate the usefulness of microdosing and AMS as a tool
for studying the pharmacokinetic characteristics, including PBMC concentrations, of
ZDV and underscore the value of AMS as a tool with which to perform pharmacokinetic
and mass balance studies using trace amounts of radiolabeled compound.
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