McGill Mitchell R, Findley David L, Mazur Anna, Yee Eric U, Allard Felicia D, Powers Allison, Coward Lori, Blough Eric R, Gorman Greg, Hambuchen Michael D
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.
Department of Pharmaceutical Science, Marshall University School of Pharmacy, Kopp Hall 353, 1 John Marshall Drive, Huntington, WV, 25755, USA.
Eur J Drug Metab Pharmacokinet. 2022 May;47(3):319-330. doi: 10.1007/s13318-022-00755-y. Epub 2022 Feb 8.
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.
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.
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.
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.
在动物模型和人类中，全身辐射暴露已被证明会改变某些药物的药代动力学，但关于辐射对精神活性药物的影响却知之甚少。在太空旅行期间、治疗性或意外辐射暴露期间或之后使用这些药物时，其药代动力学可能会发生改变，从而导致疗效降低或毒性增加。
使用甲基苯丙胺来确定急性给予1、3和6 Gy辐射对药物药代动力学和药效学的影响。雄性Wistar大鼠在第0天接受0、1、3或6 Gy的X射线辐射。在第3天测定皮下注射1 mg/kg甲基苯丙胺后的血清药代动力学。在第5天测量甲基苯丙胺诱导的（1 mg/kg）运动活性。在第6天给予甲基苯丙胺（1 mg/kg）2小时后测定脑内甲基苯丙胺浓度。在第3天和第6天评估肾脏和肝脏血清生物标志物，并在第6天进行肝脏组织学检查。
虽然血清半衰期和未变化的甲基苯丙胺尿清除率不受任何辐射剂量的影响，但在接受6 Gy辐射暴露后，甲基苯丙胺最大浓度以及血清浓度-时间曲线下0至300分钟的甲基苯丙胺和苯丙胺代谢物面积值显著降低。此外，在接受6 Gy辐射后，甲基苯丙胺诱导的运动活性以及脑内与血清甲基苯丙胺浓度之比显著升高。
虽然1至6 Gy辐射暴露不影响甲基苯丙胺的消除，但6 Gy暴露对皮下吸收和脑部分布均有影响。在辐射暴露期间或之后给药时应考虑这些影响。
