外来ぜん息患者を対象としたＳｉｎｇｌｅ Ｐｏｉｎｔ採血によるテオフィリン投与設計の検討

Abstract

It is desirable that theophylline dosage regimen is based on individual pharmacokinetic parameters for management of the outpatient with chronic asthma to avoid toxicity due to overdosage. This study was conducted to design theophylline dosage regimen by single serum sample monitoring.Four healthy volunteers were given choline theophylline 200 mg (theophylline 126.6mg) and serum theophylline concentration was measured 8 times (as specified) foi determining pharmacokinetic parameters. Average values of Ka (absorption rate constant), Vd (distribution volume), and Kel (excretion rate constant) were obtained to be 8.31/hr, 0.441 1/kg, and 0.081/hr, respectively. Individual theophylline dosage regimen was designed with these parameters. The predicted and measured concentrations of theophylline were compared with each other after multiple oral doses. The errors were within the range of -9.3 to + 12.1%. Asthmatic outpatient's Kel was calculated from single sample monitoring data and average values of Vd and Ka of healthy volunteers. Monitoring time was 4 hours after administration of choline theophylline to avoid the effect of Ka. A new dosage regimen was designed with these parameters for 14 asthmatic outpatients who had already taken theophylline. After changing dosage regimen the predicted concentrations were compared with the measured ones. The errors were within the range of -18.3 to + 18.5%, This method of theophylline dosage regimen by single serum sample monitoring is significantly useful in clinical practice to avoid the toxicity. It is applicable to design the dosage regimen of the drug with large values of Ka and Kel, and fixed value of Vd.