Aminophylline 클리어런스 및 유지 용량에 영향을 미치는 요인 분석

Abstract

In many clinical cases such as emergency bronchial asthma attack, methylxanthine bronchodilator, aminophylline may have a beneficial role in the management of asthma. However, aminophylline has a narrow therapeutic index. Also individual variability in the rates of metabolism or total clearance has marked an influence on the serum level of the drug. Generally, the overall liver function declines with age, probably as a result of reduced hepatic mass and blood flow. Therefore, we should carefully monitor mode of action and adverse effect of the drug. At present, we don't have a standard guideline for patients on maintenance dose of aminophylline. In practice, initial dose is decided by the clinical experience and maintenance dose is determined from each patient's hepatic clearance. Consequently, in the study, we aimed to analyze the factors of influencing aminophylline maintenance dose in Korean respiratory lung disease patients. From April 2004 to September 2005, the initial treatment of the patients had included constant intravenous aminophylline therapy in Seoul National University Bundang Hospital. Subjects were the adult of over 18 years old and had measured serum level in steady state. Also exclusion were made for patients with altered theophylline metabolism (e.g., smoking), drug interactions (e.g., ciprofloxacin), and concomitant disease states (e.g., congestive heart failure, liver cirrhosis). The subtherapeutic range group had smaller maintenance dose (mg/kg/hr) than the therapeutic range group (0.24 ± 0.06 vs 0.33 ± 0.12, t-test, p 0.05). Mean serum level and maintenance dose of aminophylline in therapeutic range were not influenced by sex and obesity but these were high in young subjects (less than 65 year old). No significant difference between young subjects and geriatric subjects (greater than 65yr) was detected in theophylline clearance. Also, it was found that the clearance of theophylline in obese subjects was similar to that of non-obese subjects. From this study, it is concluded that obesity (actual body weight/ideal body weight) has to be considered as the factor which affect to the clearance. Maintenance dose of the patient group reached therapeutic range was 0.33 ± 0.12 mg/kg/hr, hence dosage guideline can be set by this result.