Absorption
Theophylline is rapidly and completely absorbed in solution or immediate-release. Theophylline C max is 10 mcg/mL (range, 5 to 15 mcg/mL) and T max is 1 to 2 h. Food and antacids do no cause any clinically significant changes. The therapeutic range is 10 to 20 mcg/mL.

Distribution
Theophylline is approximately 40% protein bound (primarily to albumin). Unbound theophylline distributes throughout body water, but distributes poorly into body fat. Vd is approximately 0.45 L/kg (range, 0.3 to 0.7 L/kg) based on idea body weight. Theophylline freely passes across the placenta, into breast milk, and into CSF.

Metabolism
Theophylline does not undergo any measurable first-pass elimination. In adults and children older than 1 yr of age, about 90% of the dose is metabolized in the liver. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity.

Elimination
Excretion is via the kidneys. In neonates, approximately 50% of a theophylline dose is excreted unchanged in urine. Beyond 0 to 3 mo, 10% of a theophylline dose is excreted unchanged in urine.

Special Populations
Renal Function Impairment

No dosage adjustment is required for renal function impairment in adults and children older than 3 mo of age. In neonates with reduced renal function, dose reduction and frequent monitoring of serum concentrations is required.

Hepatic Function Impairment
A prolonged t ½ may occur in liver dysfunction.

Pharmacokinetics vary widely among similar patients and cannot be predicted by age, sex, body weight, or other demographic characteristics. A prolonged t ½ may occur in CHF, alcoholism, and respiratory infections.

Allopurinol, nonselective beta-blockers, calcium channel blockers, cimetidine, oral contraceptives, corticosteroids, disulfiram, ephedrine, influenza virus vaccine, interferon, macrolide antibiotics (eg, erythromycin), mexiletine, quinolone antibiotics (eg, ciprofloxacin), thyroid hormones
Increase theophylline levels.

Aminoglutethimide, barbiturates, hydantoins, ketoconazole, rifampin, smoking (cigarettes and marijuana), sulfinpyrazone, sympathomimetics
Decrease theophylline levels.

Benzodiazepines and propofol
Theophylline may antagonize sedative effects.

Beta-agonists
CV adverse reactions may be additive. However, may be used together for additive beneficial effects.

Carbamazepine, isoniazid, and loop diuretics
May increase or decrease theophylline levels.

Halothane
Coadministration has caused catecholamine-induced arrhythmias.

Ketamine
Coadministration may result in seizures.

Lithium
Theophylline may reduce lithium levels.

Nondepolarizing muscle relaxants
Theophylline may antagonize neuromuscular blockade.