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정상 성인에서의 Theophylline의 약동학 및 대사에 관한 연구
최혜란,신상구,이광수 중앙대학교 의과대학 의과학연구소 1989 中央醫大誌 Vol.14 No.2
Theophylline kinetics and metabolism following single intravenous infusion of theophylline dose (6mg/kg) were examined in 8 young non-smoking adults. Study design stressed stringent control of several external factors known to influence theophylline metabolism. The concentrations of theophylline were analyzed over a 24-hr period in plasma. Theophylline and its major metabolites were measured over a 96-h period in urine after the given dose. A 2-compartment model was required to describe the theophylline plasma concentration time course in all 8 subjects. The results are as follows. 1. Theophylline is quickly transferred from plasma to tissue with high rates of intercompartmental clearance (mean ±S.D; 1.04 ± 0.53 L/min). Steady-state volume of distribution of theophylline showed little intersubject variability with average of 0.42 ± 0.02 L/kg. 2. The elimination half-life of theophylline varied greatly among subjects and ranged from 4.56 to 11. 11 hours, Similarly, the non-renal clearance also showed wide intersubject variation (coeffient of variation; 35%). 3. The unbound fraction of theophylline was 62.6 ± 4.1% at the plasma concentration around 10 ㎍/ml. 4. About 82% of theophylline administered was recovered until 96-hr after dose as unchanged form or major metabolites. A 17.55% of theophylline was excreted in urine as unchanged form. Molar fraction of theophylline metabolites 1.3-dimethyl uric acid, 3-methylxanthine and 1-methyl uric acid excreted in urine were 35.14%, 11.62% and 17.64%, respectively. From the above results, It is suggested that great variation of theophylline elimination half-life seems to be mainly due to wide intersubject variation of non-renal clearance of theophylline. Importance of including an assessment of plasma protein binding in studies of theophylline disposition would be emphasized, because theophylline metabolism showed a restrictive pattern. Incomplete recovery of theophylline from the administered dose imply the possbility of exsistence of additional minor pathways in theophylline disposition, which could not be identified in the study.