Mitchell R McGill1, David L Findley2, Anna Mazur3, Eric U Yee4, Felicia D Allard4, Allison Powers5, Lori Coward6, Eric R Blough2, Greg Gorman6, Michael D Hambuchen7. 1. Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Little Rock, AR, 72205, USA. 2. Department of Pharmaceutical Science, Marshall University School of Pharmacy, Kopp Hall 353, 1 John Marshall Drive, Huntington, WV, 25755, USA. 3. Department of Biomedical Science, Marshall University School of Medicine, 1 John Marshall Drive, Huntington, WV, 25755, USA. 4. Department of Pathology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. 5. Office of Radiation Safety, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755, USA. 6. Department of Pharmaceutical, Social and Administrative Sciences, Samford University McWhorter School of Pharmacy, 800 Lakeshore Drive, Birmingham, AL, 35229, USA. 7. Department of Pharmaceutical Science, Marshall University School of Pharmacy, Kopp Hall 353, 1 John Marshall Drive, Huntington, WV, 25755, USA. hambuchen@marshall.edu.
Abstract
BACKGROUND AND OBJECTIVES: Whole-body radiation exposure has been shown to alter the pharmacokinetics of certain drugs in both animal models and humans, but little is known about the effect of radiation on psychoactive medications. These drugs may have altered pharmacokinetics when administered during or after space travel or therapeutic or accidental radiation exposure, resulting in reduced efficacy or increased toxicity. METHODS: Methamphetamine was used to determine the effects of acutely administered 1, 3, and 6 Gy radiation on drug pharmacokinetics and pharmacodynamics. Male Wistar rats were exposed to 0, 1, 3, or 6 Gy X-ray radiation on day 0. The serum pharmacokinetics of subcutaneously administered 1 mg/kg methamphetamine was determined on day 3. Methamphetamine-induced (1 mg/kg) locomotor activity was measured on day 5. Brain methamphetamine concentrations were determined 2 h after methamphetamine administration (1 mg/kg) on day 6. Renal and hepatic serum biomarkers were assessed on days 3 and 6, with liver histology performed on day 6. RESULTS: While serum half-life and unchanged methamphetamine urine clearance were unaffected by any radiation dose, maximum methamphetamine concentrations and methamphetamine and amphetamine metabolite area under the serum concentration-time curve values from 0 to 300 min were significantly reduced after 6 Gy radiation exposure. Additionally, methamphetamine-induced locomotor activity and the brain to serum methamphetamine concentration ratio were significantly elevated after 6 Gy radiation. CONCLUSIONS: While 1-6 Gy radiation exposure did not affect methamphetamine elimination, 6 Gy exposure had effects on both subcutaneous absorption and brain distribution. These effects should be considered when administering drugs during or after radiation exposure.
BACKGROUND AND OBJECTIVES: Whole-body radiation exposure has been shown to alter the pharmacokinetics of certain drugs in both animal models and humans, but little is known about the effect of radiation on psychoactive medications. These drugs may have altered pharmacokinetics when administered during or after space travel or therapeutic or accidental radiation exposure, resulting in reduced efficacy or increased toxicity. METHODS: Methamphetamine was used to determine the effects of acutely administered 1, 3, and 6 Gy radiation on drug pharmacokinetics and pharmacodynamics. Male Wistar rats were exposed to 0, 1, 3, or 6 Gy X-ray radiation on day 0. The serum pharmacokinetics of subcutaneously administered 1 mg/kg methamphetamine was determined on day 3. Methamphetamine-induced (1 mg/kg) locomotor activity was measured on day 5. Brain methamphetamine concentrations were determined 2 h after methamphetamine administration (1 mg/kg) on day 6. Renal and hepatic serum biomarkers were assessed on days 3 and 6, with liver histology performed on day 6. RESULTS: While serum half-life and unchanged methamphetamine urine clearance were unaffected by any radiation dose, maximum methamphetamine concentrations and methamphetamine and amphetamine metabolite area under the serum concentration-time curve values from 0 to 300 min were significantly reduced after 6 Gy radiation exposure. Additionally, methamphetamine-induced locomotor activity and the brain to serum methamphetamine concentration ratio were significantly elevated after 6 Gy radiation. CONCLUSIONS: While 1-6 Gy radiation exposure did not affect methamphetamine elimination, 6 Gy exposure had effects on both subcutaneous absorption and brain distribution. These effects should be considered when administering drugs during or after radiation exposure.
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