THEOPHYLLINE

... Bronchodilator Effect Compared With That of Salbutamol Although salbutamol (albuterol) 200mg by inhalation produced significantly greater bronchodilatation (FEV1 ) than theophylline 375mg orally for the first 30 minutes of a double-blind crossover trial in 14 asthmatics, the total mean effects of each drug over the 6 hour study did not differ significantly.

The 14 hospitalised patients aged between 28 and 67 years had partially reversible airways obstruction due either to asthma or chronic bronchitis with asthma, which was in a steady state. The medications were given at the same time in the morning on two separate days'and comprised 375mg theophylline orally plus a placebo aerosol or 200J.Lg salbutamol by inhalation plus placebo tablets. Sympathomimetic and xanthine drugs were withdrawn 12 hours prior to the study, but maintenance doses of oral or aerosol corticosteroids and sodium cromoglycate were continued. Ventilatory response was determined by measuring FEV1 and expressed as the percentage increase from the baseline value.

Salbutamol produced significantly greater bronchodilatation than theophylline for the initial 30 minutes, but there was no significant difference from 60 to 240 minutes. A significantly greater response in favour of theophylline was present at· 360 minutes. Based on the area under the FEV 1 response curves there was no significant difference in the total mean responses for salbutamol (144.06 ± 25.70) or theophylline (135.91 ± 17 .78).

'If both drugs were administered simultaneously, it is possible that the beneficial bronchodilator properties of each drug may be additive ... whether such a prediction could be realised without producing significant toxicity requires further investigation. '

Hartnett, B.J.S. and Marlin, G.E.: British Journal of Clinical Pharmacology 3: 591 (Aug 1976)

... Renal Clearance The renal clearance of theophylline was found to decrease from 8.50 ± 2.20 to 2.76 ± 1.13rnl/min/m2 during 8 hours after oral administration of a single dose of 200mg/m2 in solution.

The 12 experiments in 6 healthy adult subjects indicated a highly significant positive correlation between the renal clearance of theophylline and the urine flow rate for each subject. There was no consistent correlation between renal clearance and plasma concentrations of theophylline. As renal excretion is only a minor pathway of theophylline elimination in man, urine flow rate-dependent changes in the renal clearance of the drug will have only a small effect on its kinetics of elimination.

Levy, G. and Koysooko, R.: Journal of Clinical Pharmacology 16: 329 (Jull976)