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Effects of Hind Limb Unloading on Pharmacokinetics of Procainamide in MiceThe pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in space. It is prudent to expect that low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration. Among the medications of special interest are the cardiovascular drugs, especially the antiarrhythmic agents. In this study we used hind limb unloaded (HLU) mice as a model to investigate possible changes in the PK of a common antiarrhythmic drug procainamide (PA). Prior to drug administration the experimental animals were tail suspended for 24 hours and the control animals were kept free. PA (150-250 mg per kg) was given orally by a gavage procedure. After that the experimental mice were kept suspended for additional 1, 2, 3 and 6 hours. At these time points the serum concentration of PA and N-acetyl-procainamide (NAPA), an active metabolite which is formed by N-acetyltransferase in the liver, were measured by the fluorescence polarization immunoassay (FPIA) on the AxSYM autoanalyzer (Abbott Laboratories, Abbott Park, IL). The serum level of PA in HLU mice at 1 hour after administration was almost 40% lower than in controls. At 2-3 hours the difference still maintained, however, it was not statistically significant; at 6 hours no difference was detected. The level of NAPA in HLU mice was slightly lower at 1 and 2 hours but the difference did not reach statistical significance. The estimated PA half-life time in HLU mice was almost 55% longer than in control animals. These results confirm that hind limb unloading and related hemodynamic changes significantly alter the PK of PA. The effects are most likely primarily associated with a decrease in the drug absorption, especially within the first two hours after administration. At the same time prolongation of the PA half-life time in the HLU mice points towards slower drug elimination from the circulation.
Document ID
20070029284
Acquisition Source
Johnson Space Center
Document Type
Conference Paper
Authors
Risin, Semyon A.
(Texas Univ. Health Science Center Houston, TX, United States)
Dasgupta, Amitava
(Texas Univ. Health Science Center Houston, TX, United States)
Ramesh, Govindarajan T.
(Texas Univ. Houston, TX, United States)
Risin, Diana
(NASA Johnson Space Center Houston, TX, United States)
Date Acquired
August 23, 2013
Publication Date
January 1, 2007
Subject Category
Aerospace Medicine
Meeting Information
Meeting: 79th Annual Scientific Meeting of the Aerospace Medical Association
Location: Boston, MA
Country: United States
Start Date: May 11, 2008
End Date: May 15, 2008
Sponsors: Aerospace Medical Association
Distribution Limits
Public
Copyright
Other

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