Theophylline 제제의 정맥주입 후 경구전환 시 겉보기 클리어런스 저하 원인 분석

Abstract

Theophylline is a bronchodilator that is required therapeutic drug monitoring (TDM) for its narrow therapeutic range. The clearance of oral theophylline should not decreased in case of changing the administration route from intravenous to oral, because oral theophylline was known as being absorbed almost all for its high lipid solubility. But decrease of clearance was observed in a lot of TDM cases in Seoul National University of Hospital (SNUH). This study was designed to analyze factors that affect the decrease of clearance. Patients were enrolled who had blood samples which gathered for measuring theophylline level at SNUH from January 2002 to June 2003 more than two times. Two factors that were analyzed out are accuracy of concentration of aminophylline diluted solution and accuracy of volume that were injected through the infusion pump. The extent of the decrease of clearance was 16.7 ± 17.5%(-0.8~34.2%) as average after changing the administration route. The mean volume errors of aminophylline ampule were 11.1 ± 0.3% and the mean volume errors of each dextrose 5%, 10% solution were inside of the Korean Pharmacopoeia standard. The errors of injected volume through a infusion pump were -4.4 ± 4.7%(-9.1~0.3%). As a result, real amount of aminophylline diluted solution was different with represented amount, the extent of the difference was -15.3~10.2%. More deviation caused by errors in process of preparation of aminophylline diluted solution or by mechanical troubles of infusion pump was also expected. The follow up TDM of oral theophylline is not always required after the change of administration route from intravenous to oral. But this study suggested that the errors of the concentration and the deviations of the injected volume of aminophylline diluted solution. This study also gave evidences to the decrease of parenteral clearance of oral theophylline after the change of administration route. Therefore dose modification of oral theophylline is needed after the change of administration route form intravenous to oral by means of follow up TDM.