Dược Động Học :
▧ Absorption :
Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.
▧ Volume of Distribution :
* 0.3 to 0.7 L/kg
▧ Protein binding :
40%, primarily to albumin.
▧ Metabolism :
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.
▧ Route of 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.
▧ Half Life :
▧ 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]