Usefulness and safety of theophylline injection form (Theodrip) for the treatment of acute asthma.

The effects of the speed of intravenous infusion on the pharmacokinetics of theophylline were studied in 9 healthy volunteers (Ex I). Subjects were intravenously administered either six 4.8 mg/kg theophylline (Theodrip®, Nikken Chemicals Co., Ltd., Japan) or three matching placebo injections (4.8 ml/kg physiological saline) for 30 min (Step I) or for 15 min (Step II). In Steps I and II, C max was 10.8 ± 1.1 and 10.8 ± 0.8 μg/ml, respectively. These C max s were concentrations yielding therapeutic effects in patients with acute asthma. Next, comparative pharmacokinetics between theophylline (Theodrip®) and aminophylline were examined by a crossover method in 16 healthy volunteers (Ex II). The 90% confidence limits of the differences of mean values were within 80-120% and were 92.8-100.1% for C max , 99.7-105.3% for t 1/2 and 100.2-104.4% for AUC. Thus, we concluded that the pharmacokinetics of the plasma theophylline after intravenous administration of Theodrip® (theophylline at 4.8 mg/kg) were bioequivalent to those of aminophylline (6.0 mg/kg) for 30 min. In Ex I and II, no subjects had adverse effects and in Ex I no influence on ECG was seen. In addition, the convenience of Theodrip® was compared with that of ampules of aminophylline among nurse volunteers (Ex III). The times required for set-up of Theodrip® were significantly shorter than those of aminophylline ampules. On the other hand, the adverse reactions to aminophylline resulting from hypersensitivity reactions to its ethylenediamine component have been reported. Theodrip® consists of 200 mg theophylline and 200 ml physiological saline in a plastic bag. Therefore. Theodrip®, which does not contain ethylendiamine, is expected to have less adverse effects and be easier to handle than aminophylline.