EVALUATION OF DRUG METABOLIZING STATUS BY CARBON DIOXIDE BREATH TESTS

通过二氧化碳呼气试验评价药物代谢状态

• 批准号: 3821238
• 负责人: E A LANE
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3821238
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; brain disorder chemotherapy; breath tests; carbon dioxide; drug metabolism; epilepsy; gastrointestinal drug absorption; human subject; liver metabolism; mass spectrometry

Preliminary testing of the prediction that caffeine, a low extraction ration drug (0.1) should be a more sensitive probe of enzyme induction than methacetin, a high extaraction ratio drug (0.9), when excretion of a metabolite (CO2) is measured, has been carried out. A single dose of each was administered to 8 healthy volunteers and 9 epilepsy patients treated with phenytoin, carbamazepine and/or phenobarbital. The 13C carbon dioxide in expired breath was measured by isotope ratio mass spectrometry. The percentages of the dose excreted as CO2 in 2 hr. were compared: 3.22% pus minus 0.86 and 5.54% plus minus 1.59 caffeine was excreted by controls and patients, respectively, compared with 28.6% plus minus 5.8 and 40.0% plus minus 4.2 methacetin. The results in the 2 subject groups were significantly different for both probes (P less than .05). These data do not support the theoretical prediction that the extraction ratio of a drug has a critical effect upon its usefulness in detection of induction of oxidative metabolism via the carbon dioxide breath test. The pharmacokenetics of ethanol have been studied by measurement of blood ethanol concentrations during and after four oral dosing rates and one intravenous infusion to four healthy volunteers. The consumption of breakfast after two hours of oral dosing disrupted the smooth approach to steady state concentrations which cannot be explained as a simple delay in absorption. The data indicate a significant effect of food upon the bioavailability of ethanol probably due to increase in stomach emptying time.

初步测试的预测，咖啡因，低 提取比药物（0.1）应该是一个更敏感的探针， 酶诱导比美沙西丁，高提取率药物 (0.9)当测量代谢物（CO2）的排泄时， 贯彻 8名健康受试者接受了单剂量的每种药物。 志愿者和9名用苯妥英治疗的癫痫患者， 卡马西平和/或苯巴比妥。 13C二氧化碳在 通过同位素比率质谱法测量呼出的呼吸。 2小时内以CO2形式排泄的剂量百分比为 比较：3.22%脓减0.86和5.54% ± 1.59 咖啡因分别由对照组和患者排出， 相比之下，28.6%的正负5.8和40.0%的正负4.2 美沙西丁 2个受试者组的结果显著 两种探头的差异（P <0.05）。 这些数据不 支持理论预测，即 药物在检测中的有效性具有关键作用， 通过二氧化碳呼吸诱导氧化代谢 test. 乙醇的动力学已被研究， 在治疗期间和治疗后测量血液乙醇浓度 四个口服剂量率和一个静脉输注，以四个健康 志愿者 早餐食用后两小时口服 给药破坏了稳态的平稳接近 浓度不能解释为一个简单的延迟， 吸收 数据表明，食物对 乙醇的生物利用度可能是由于胃中的增加 清空时间