Drug Groups

approved

Description

A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-cyclic nucleotide phosphodiesterase that degrades cyclic AMP thus potentiates the actions of agents that act through adenylate cyclase and cyclic AMP. [PubChem]

Indication

For the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, such as emphysema and chronic bronchitis.

Pharmacology

Theophylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Theophylline has two distinct actions in the airways of patients with reversible (asthmatic) obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects).

Toxicity

Symptoms of overdose include seizures, arrhythmias, and GI effects.

Affected Organisms

Biotransformation

Hepatic. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1-methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a theophylline dose is N-methylated to caffeine. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity.

Absorption

Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.

Half Life

8 hours

Protein Binding

40%, primarily to albumin.

Elimination

Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults.

Distribution

* 0.3 to 0.7 L/kg

Clearance

* 0.29 mL/kg/min [Premature neonates, postnatal age 3-15 days]
* 0.64 mL/kg/min [Premature neonates, postnatal age 25-57 days]
* 1.7 mL/kg/min [Children 1-4 years]
* 1.6 mL/kg/min [Children 4-12 years]
* 0.9 mL/kg/min [Children 13-15 years]
* 1.4 mL/kg/min [Children 16-17 years]
* 0.65 mL/kg/min [Adults (16-60 years), otherwise healthy non-smoking asthmatics]
* 0.41 mL/kg/min [Elderly (>60 years), non-smokers with normal cardiac, liver, and renal function]
* 0.33 mL/kg/min [Acute pulmonary edema]
* 0.54 mL/kg/min [COPD >60 years, stable, non-smoker >1 year]
* 0.48 mL/kg/min [COPD with cor pulmonale]
* 1.25 mL/kg/min [Cystic fibrosis (14-28 years)]
* 0.31 mL/kg/min [Liver disease cirrhosis]
* 0.35 mL/kg/min [acute hepatitis]
* 0.65 mL/kg/min [cholestasis]
* 0.47 mL/kg/min [Sepsis with multi-organ failure]
* 0.38 mL/kg/min [hypothyroid]
* 0.8 mL/kg/min [hyperthyroid]

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