Aminophylline

Aminophylline is a soluble derivative of theophylline and is given for its theophylline activity.

Aminophylline relaxes smooth muscle and relieves bronchial spasm. It stimulates the myocardium and reduces venous pressure in congestive heart failure, leading to a marked increase in cardiac output.

It has stimulant effect on respiration, and also a diuretic action of short duration.

Absorption

Following oral administration of PHYLLOCONTIN CONTINUS tablets, the delivery of theophylline is controlled and at steady state, peak concentrations are typically seen after approximately 5 hours.

An effective plasma concentration is considered to be 5-12 micrograms/ml, although plasma concentrations up to 20 micrograms/ml may be necessary to achieve efficacy in some cases. Do not exceed 20 micrograms/ml.

Distribution and Protein Binding

Theophylline is distributed through all body compartments; approximately 60 % is bound to plasma proteins

Biotransformation

Theophylline is metabolised in the liver to 1,3 dimethyluric acid, 1 methyluric acid and 3-methylxanthine.

Elimination

Theophylline and its metabolites are excreted mainly in the urine. Approximately 10% is excreted unchanged.

Factors affected clearance

The predominant factors which alter theophylline clearance are: age, body weight, diet, smoking habits, other drugs and cardiorespiratory or hepatic disease. Clearance is increased in children compared to values observed in adult subjects. Clearance decreases towards adult values in late teens.

Genotoxicity and Carcinogenicity

In vitro and in vivo assays, have shown both positive and negative genotoxic results for theophylline. However, oral theophylline administered daily to rats and mice for 2 years did not show carcinogenicity. Therefore, it is unlikely that theophylline poses a carcinogenic risk in man.

Reproductive and Developmental Toxicity

Theophylline has been shown to have effects upon the male reproductive system in rodents, but a doses considered in excess of the maximum human dose indicating little relevance to clinical use.

Several embryofetal development studies in rats, mice and rabbits have demonstrated developmental effects independent from maternal toxicity at high dose of theophylline. Therefore theophylline should be considered to have the potential for developmental toxicity in man.