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Pharmacokinetics of Acetaminophen in Hind Limbs Unloaded Mice: A Model System Simulating the Effects of Low Gravity on Astronauts in Space
Author and Affiliation:
Peterson, Amanda(Texas Univ. Health Science Center, Houston, TX, United States)
Risin, Semyon A.(Texas Univ. Health Science Center, Houston, TX, United States)
Ramesh, Govindarajan T.(Texas Southern Univ., Houston, TX, United States)
Dasgupta, Amitava(Texas Univ. Health Science Center, Houston, TX, United States)
Risin, Diana(NASA Johnson Space Center, Houston, TX, United States)
Abstract: The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in Space. 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 in astronauts. Acquiring of such knowledge has inherent difficulties due to limited opportunities for experimenting in Space. One of the approaches is to use model systems that simulate some of the Space conditions on Earth. In this study we used hind limbs unloaded mice (HLU) to investigate the possible changes in PK of acetaminophen, a widely used analgesic with high probability of use by astronauts. The HLU is recognized as an appropriate model for simulating the effects of low gravity on hemodynamic parameters. Mice were tail suspended (n = 24) for 24-96 hours prior to introduction of acetaminophen (150 - 300 mg/kg). The drug (in aqueous solution containing 10% ethyl alcohol by volume) was given orally by a gavage procedure and after the administration of acetaminophen mice were additionally suspended for 30 min, 1 and 2 hours. Control mice (n = 24) received the same dose of acetaminophen and were kept freely all the time. Blood specimens were obtained either from retroorbital venous sinuses or from heart. Acetaminophen concentration was measured in plasma by the fluorescent polarization immunoassay and the AxSYM analyzer (Abbott Laboratories). In control mice peak acetaminophen concentration was achieved at 30 min. By 1 hour the concentration decreased to less than 50% of the peak level and at 2 hours the drug was almost undetectable in the serum. HLU for 24 hours significantly altered the acetaminophen pharmacokinetic: at 30 min the acetaminophen concentrations were significantly (both statistically and medically significant) lower than in control mice. The concentrations also reduced less significantly after 1 and 2 hours. At 2 hours approximately 20% of the drug still remained in the circulation. After 96 hrs of HLU the changes in acetaminophen PK were less prominent. These data indicate that short term HLU causes significant changes in acetaminophen PK most likely associated with HUL-related hemodynamic changes. However, after 96 hour these changes diminished. This suggests hemodynamic adaptation to the HUL conditions that possibly occurs also in real space conditions.
Publication Date: Jan 01, 2008
Document ID:
20080012544
(Acquired Mar 12, 2008)
Subject Category: AEROSPACE MEDICINE
Document Type: Conference Paper
Meeting Information: 43rd Annual ACLPS Meeting; 5-7 Jun. 2008; Philadelphia, PA; United States
Meeting Sponsor: Academy of Clinical Laboratory Physicians and Scientists; United States
Financial Sponsor: NASA Johnson Space Center; Houston, TX, United States
Organization Source: Texas Univ. Health Science Center; Houston, TX, United States
NASA Johnson Space Center; Houston, TX, United States
Description: 2p; In English
Distribution Limits: Unclassified; Publicly available; Unlimited
Rights: Copyright
NASA Terms: PHARMACOLOGY; HEMODYNAMIC RESPONSES; GRAVITATIONAL EFFECTS; AQUEOUS SOLUTIONS; PLASMAS (PHYSICS); MICROGRAVITY; METABOLISM; IMMUNOASSAY; EXCRETION; SIMULATION; PROBABILITY THEORY; FLUORESCENCE
Availability Source: Other Sources
Availability Notes: Abstract Only
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