Intravenous administration of enprofylline to asthmatic patients

Abstract

In 6 asthmatic patients, the possibility of obtaining a steady state plasma level of 5 mg/l of enprofylline by administration of two constant rate infusions was examined. The simulated plasma concentration curves, based on information from preassessment of individual pharmacokinetic parameters, were in good agreement with the plasma levels obtained. The side-effects and bronchodilatation produced by enprofylline were compared to those obtained with theophylline at a steady state level of 15 mg/l. Enprofylline and theophylline caused a mean maximal increase in FEV1.0 of 14% and 2.6% per mg/l in plasma, respectively. Side-effects, headache, nausea and vomiting, became pronounced in 2 patients in whom the plasma enprofylline level was about 6 mg/l. No other serious adverse reaction was seen. It is suggested that enprofylline should be further evaluated as a possible anti-asthmatic drug.

Structure-activity relationship in N3-alkyl-xanthine derivatives.

“…The results of this study indicated that the potencies of the relaxant effect of two different alkylxan thine derivatives (butyl and isobutylxan thines) are nearly equal to that of propylxan thine. Propylxanthine has been found to be 4-5 times more potent than theophylline both in vitro and in vivo (4,17,18). Our in vitro study using guinea pig tracheal smooth mus cle preparations also indicated that propyl xanthine is approximately 6-fold more potent than theophylline.…”

Maximally effective plasma concentrations of enprofylline and theophylline during constant infusion.

“…Preclinical results show that enprofylline is about five times more potent compared to theophylline in relaxing airway smooth muscle contracted by various tentative asthma mediators (Finney et al, 1984). This potency relation of one to five has been found in evaluation of bronchodilating properties of the two drugs in asthmatic patients (Laursen et al, 1983b;Lunell et al, 1982Lunell et al, , 1983) and a ratio of one to four in effects of xanthines on allergen induced bronchoconstriction in patients with allergic asthma (Van der Straeten et al, 1983). This examination was undertaken at a plasma concentration ratio of approximately one to four between enprofylline and theophylline.…”

“…, (Borga et al, 1983;Edholm, 1980). The methods for calculation of basic pharmacokinetic parameters and infusion rates were the same as previously described (Laursen et al, 1983b). The comparison between enprofylline, theophylline, and placebo took place on three different days.…”

Enprofylline and Theophylline Slow-Eroding Tablets in the Treatment of Asthma: A Comparison

“…Enprofylline (3-propyl-xanthine) is about 3-5 times as potent in its antiasth matic effects as theophylline when given as a single dose [1][2][3]. It is also free of some extrapulmonary effects produced by theo phylline such as CNS-stimuiant behav ioral effects, e.g.…”

“…convulsions and seizures, diuretic actions and gastrointestinal irri tant effects [4][5][6]. After the administration of single doses, enprofylline may induce dose-related transient headaches and nau sea [1,2,7], Because of the short half-life of enprofylline (about 2 h), a sustained re lease preparation of the drug was devel oped, which can be given twice daily for long-term treatment. The present study was performed in order to compare the antiasthmatic effects and side-effects of a continuous 14-day enprofylline adminis tration with theophylline treatment.…”