In this study we examined the efficacy and pharmacokinetics of a new chrono-optimized theophylline sustained release preparation for once-daily dosing in the evening for treating bronchial asthma. In a randomized, open crossover study, Euphylong (administered once daily at 2000 hours) was compared with the same dose of a reference preparation (subdivided into two equal doses taken at 800 and 2000 hours). Administration and dosage were in accordance with prior determination of clearance. The patients were outpatients during the first six days of every phase, whereas for the following 24-hour measurement period they were admitted as inpatients for measuring the requisite pharmacokinetic and pharmacodynamic data (PEF, FEV1, PEF 25 = 75, FVC). The theophylline levels remained practically constant for 24 hours under conventional theophylline treatment with twice-daily administration. In contrast, the variations of the theophylline serum levels and the night levels were higher after once-daily dosage of Euphylong, and the daytime levels and especially at the end of the dosage interval were lower. Compared with the standard profile without medication, both sustained release preparations improved the airway obstruction significantly and comparably during a 24-hour period. However, in the early morning hours between 200 and 600 both PEF and FEV1 were significantly higher under Euphylong. Between the improvement of PEF and FEV1 and the theophylline serum concentrations there was a significant correlation between 200 and 600 under Euphylong only. It is concluded that the treatment of asthma with the chrono-optimized once-daily theophylline preparation Euphylong over night is more effective than treatment with a conventional preparation in twice-daily dosage.

Adult↗

PubMed1991

[Efficacy of a theophylline retard preparation administered at 3 different intake times additionally to basic medication].

In this randomised crossover study in 26 outpatients with bronchial asthma the efficacy of a new once-daily theophylline formulation given in addition to a baseline medication was investigated; moreover, under steady state conditions, the effect of three evening intake times (6, 8 and 10 p.m.) on 24-hour pharmacokinetics and peak-expiratory flow profiles was evaluated. The theophylline dose had been individually titrated. The pharmacodynamic results show a marked improvement in 24-hour lung function data after adding theophylline to a drug therapy including inhalative anti-cholinergics in 50% of the treated outpatients. No significant differences between the pharmacokinetic characteristics and the 24-hour averages (mesors) of peak expiratory flow at the three different intake times 6, 8 and 10 p.m. were found; however, intake at 10 p.m. resulted in the highest nocturnal excess of serum theophylline concentrations and the highest peak expiratory flow during the early morning hours between 2 and 6 a.m.

Adult↗

PubMed1991

[Long-term stability of morning serum theophylline level in asthma patients under minimally 1-year therapy with Euphylong].

The long-term stability of morning serum theophylline concentrations (STC) and peak expiratory flow (PEF) was investigated for at least one year in 21 asthmatic patients who received individualised theophylline doses in addition to a baseline medication (beta 2-agonists, corticosteroids, anticholinergics by MDI). All patients had previously participated in a randomised crossover study with the new sustained-release theophylline formulation Euphylong, so that 24-hour steady-state STC profiles were available. During the 15 (13-18) months' follow-up, the theophylline dose was increased by about 6% on average; the largest increase of 33% (from 750 mg to 1000 mg) occurred in 4 patients. The morning STCs between 8 and 9 a.m. were intra-individually averaged over the longest interval with a constant dose; median and range were 11.6 (9.7-15.8) mg/l. The coefficient of variation was less than 10% in 8 patients and between 11 and 20% in 10 patients. The corresponding peak-flow values were 474 (239-622) l/min with a coefficient of variation of up to 10% in 16 patients and between 11 and 20% in 3 patients. The long-term study over more than one year confirmed the reproducibility of the Euphylong plateau profile previously found in controlled short-term pharmacokinetic studies and clinical trials.

Adult↗

PubMed1990

Efficacy of sustained release theophylline given at three different evening intake times in addition to a baseline medication.

In this randomized crossover study of 26 outpatients with bronchial asthma the efficacy of a new once-daily theophylline formulation given in addition to a baseline medication was investigated; moreover, under steady state conditions, the effect of three evening intake times (6, 8 and 10 p.m.) on 24 h pharmacokinetics and peak-expiratory flow profiles was evaluated. The theophylline dose had been individually titrated. The pharmacodynamic results show a marked improvement of 24 h peak expiratory flow values after adding theophylline to a drug therapy including inhalative beta 2-agonists and corticosteroids in nearly all and inhalative anticholinergics in 50% of the treated outpatients. No significant differences between the pharmacokinetic characteristics and the 24 hr averages (mesors) of peak expiratory flow at the three different intake times 6, 8 and 10 p.m. were found; however, intake at 10 p.m. resulted in the highest nocturnal excess of serum theophylline concentrations and the highest peak expiratory flow during the early morning hours between 2 and 6 a.m.

Asthma↗