Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol.
Factors affecting theophylline clearances: age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol.
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影响茶碱清除率的因素：年龄、烟草、大麻、肝硬化、充血性心力衰竭、肥胖、口服避孕药、苯二氮卓类药物、巴比妥类药物和乙醇。
DOI：
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发表时间：
1979
期刊：
影响因子：
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通讯作者：
J. Vance
中科院分区：
文献类型：
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作者：
W. Jusko;M. Gardner;A. Mangione;Jerome J. Schentag;J. Koup;J. Vance
通过监测成年肺病患者的茶碱治疗，以及对儿科患者、正常志愿者和其他疾病患者的特殊研究，系统地收集了药代动力学、病理生理学和历史数据。通过输注剂量后的非线性计算机分析或单次口服或静脉注射茶碱剂量后的曲线下面积数据估计总清除率（ClT）。ClT值主要反映茶碱的生物转化率，平均为58（±30）ml/hr/kg，范围为4 ~ 143 ml/hr/kg。影响茶碱ClT的因素包括年龄；性;肝脏疾病;充血性心力衰竭；肥胖;肾功能;药物、烟草、大麻、咖啡因或酒精使用史；和怀孕。采用NYBAID（自动交互检测器）计算机程序进行方差分析，确定与ClT相关的自变量的顺序、优先级和组合。影响该人群中茶碱ClT的主要因素包括年龄、肝脏疾病、吸烟状况和充血性心力衰竭。年龄与ClT有很强的相关性（r = - 0.49）。在特定的亚组中有更多的变异性。例如，年轻成人（20-40岁）大麻使用者表现出最高的ClT值（83±29 ml/hr/kg），而老年肝病患者（50 -40岁）的代谢率最低（22±10 ml/hr/kg）。在特定的主题类型中，性行为（青少年）、口服避孕药（吸烟者）、肥胖（年轻非吸烟者）和巴比妥类药物也会影响茶碱的倾向。相比之下，一些常见的因素，如慢性茶碱、慢性皮质类固醇、咖啡因、性（成人）和怀孕没有改变茶碱ClT。-这种独特的临床药代动力学监测和统计方法用于患者的药物清除率表征，允许以一种可能对药物处置率和剂量方案预测有用的格式确定标准。
Pharmacokinetic, pathophysiologic, and historic data were systematically collected while monitoring theophylline therapy in adult pulmonary patients and from special studies in pediatric patients, normal volunteers, and patients with other diseases. Total body clearances (ClT) were estimated by nonlinear computer analysis after infusion dosage or from area under the curve data following single oral or intravenous theophylline doses. The ClT values, primarily reflecting the theophylline biotransformation rate, averaged 58 (±30) ml/hr/kg and ranged from 4 to 143 ml/hr/kg. Factors examined for their effect on theophylline ClT included age; sex; liver disease; congestive heart failure; obesity; renal function; history of drug, tobacco, marijuana, caffeine, or alcohol use; and pregnancy. The NYBAID (automatic interaction detector) computer program for analysis of variance was employed to determine the order, priority, and combinations of independent variables correlating with ClT. The major factors that affected theophylline ClT in this population included age, liver disease, smoking status, and congestive heart failure. Age showed strong correlation (r = −0.49) with ClT. Much additional variability was accounted for in specific subgroups. For example, young adult (20-40 years) marijuana users exhibited highest ClT vales (83 ± 29 ml/hr/kg) while older patients (>40 years) with liver disease had the lowest metabolism rates (22 ± 10 ml/hr/kg). In particular subject types, sex (in teenagers), oral contraceptives (in smokers), obesity (in young nonsmokers), and barbiturates also affected theophylline disposition. In contrast, several common factors such as chronic theophylline, chronic corticosteroids, caffeine, sex (in adults), and pregnancy did not alter theophylline ClT.- This unique clinical pharmacokinetic monitoring and statistical approach to drug clearance characterization in patients permits identification of criteria in a format that may be useful for the prediction of drug disposition rates and dosage regimens.