Feldman C H, Hutchinson V E, Sher T H, Feldman B R, Davis W J
Ther Drug Monit. 1982;4(1):69-76. doi: 10.1097/00007691-198204000-00010.
The influences on theophylline metabolism are multifactorial, resulting in significant inter- and intrapatient variability in drug responsiveness. Clinical investigations with adult patients have demonstrated the influence of diet on theophylline metabolism following a single drug dose. We have undertaken this study to examine the effect of nutritional factors on theophylline pharmacokinetics in 14 asthmatic children receiving the drug on a chronic basis. For 12-day periods each patient received three separate diets with different proportions of protein and carbohydrate but with constant fat and caloric intake. Significant differences were detected for theophylline half-life, apparent volume of distribution, and metabolic clearance rate. The high-protein diet markedly shortened the drug-elimination half-life relative to a normal diet, and high carbohydrate significantly increased it (both p less than 0.001). Other kinetic parameters confirmed this pattern. Our findings in children clearly establish that nutritional factors have a significant environmental influence on theophylline metabolism during the drug's steady-state pharmacokinetics.
对茶碱代谢的影响是多因素的，导致患者之间和患者体内药物反应性存在显著差异。针对成年患者的临床研究表明，单次给药后饮食对茶碱代谢有影响。我们开展了这项研究，以检验营养因素对14名长期接受该药物治疗的哮喘儿童茶碱药代动力学的影响。在为期12天的时间段内，每位患者接受三种不同的饮食，蛋白质和碳水化合物比例不同，但脂肪和热量摄入恒定。茶碱的半衰期、表观分布容积和代谢清除率存在显著差异。相对于正常饮食，高蛋白饮食显著缩短了药物消除半衰期，高碳水化合物饮食则显著延长了半衰期（两者p均小于0.001）。其他动力学参数也证实了这一模式。我们在儿童中的研究结果清楚地表明，在药物稳态药代动力学过程中，营养因素对茶碱代谢具有显著的环境影响。
