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 1). Subjects were intravenously administered either six 4.8 mg/kg theophylline (Theodrip(R), Nikken Chemicals Co., Ltd., Japan) or three matching placebo injections (4.8 ml/kg physiological saline) for 30 min (Step 1) or for 15 min (Step II). In Steps I and II, C-max was 10.8 +/- 0.8 mu g/ml, respectively. These C(max)s were concentrations yielding therapeutic effects in patients with acute asthma. Next, comparative pharmacokinetics between theophylline (Theodrip(R)) and aminophylline were examined by a crossover method in 16 healthy volunteers (Ex II). The90% 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 conculed that the pharmacokinetics of the plasma theophylline after intravenous administration of Theodrip(R) (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(R) was compared with that of ampules of aminophylline among nurse volunteers (Ex III). The times required for set-up of Theodrip(R) 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(R) consists of 200 mg theophylline and 200 ml physiological saline in a plastic bag. Therefore, Theodrip(R), which does not contain ethylendiamine, is expected to have less adverse effects and be easier to handle than aminophylline. (C) 2000 Prous Science. All rights reserved.