What is the recommended dose of Deriphyllin (theophylline) per kilogram for a patient with asthma or chronic obstructive pulmonary disease (COPD)?

Deriphyllin (Theophylline) Dosing Per Kilogram

For intravenous loading: 4.6 mg/kg theophylline (5.7 mg/kg as aminophylline) over 30 minutes produces an average serum concentration of 10 mcg/mL; for maintenance infusion: 0.4 mg/kg/hr in non-smoking adults or 0.8 mg/kg/hr in children age 1-9 years. 1

Loading Dose Administration

The standard loading dose is 4.6 mg/kg of theophylline (5.7 mg/kg as aminophylline) calculated on ideal body weight, administered intravenously over 30 minutes. 1 This produces a maximum post-distribution serum concentration averaging 10 mcg/mL with a range of 6-16 mcg/mL. 1

Critical Considerations Before Loading:

• Do not give a loading dose if the patient has received any theophylline in the previous 24 hours without first obtaining a serum level. 1
• If prior theophylline use is confirmed, calculate the loading dose as: D = (Desired C - Measured C) × 0.5 L/kg, where desired concentration should be conservative at 10 mcg/mL. 1
• Each mg/kg administered increases serum concentration by approximately 2 mcg/mL on average. 1

Maintenance Infusion Rates

After the loading dose, initiate continuous infusion based on patient population:

Non-Smoking Adults:

• 0.4 mg/kg/hr theophylline (0.5 mg/kg/hr as aminophylline) achieves steady-state of 10 mcg/mL (range 7-26 mcg/mL). 1

Children Age 1-9 Years:

• 0.8 mg/kg/hr theophylline (1.0 mg/kg/hr as aminophylline) achieves similar steady-state concentrations. 1

Elderly Patients (>60 years):

• Reduce dose by 30% as clearance decreases by an average of 30% compared to young adults. 1

Patients with Hepatic Insufficiency or CHF:

• Reduce dose by 50% or more as clearance is decreased by 50% or more in these populations. 1

Smokers:

• May require higher doses as tobacco smoking increases theophylline clearance through metabolic pathway induction. 1

Therapeutic Monitoring Algorithm

Obtain serum theophylline concentration 30 minutes after loading dose completion to assess need for additional loading and guide continuing therapy. 1

Obtain second serum concentration one expected half-life after starting constant infusion:

• Approximately 4 hours in children age 1-9 years 1
• Approximately 8 hours in non-smoking adults 1

Target therapeutic range: 5-15 mcg/mL for optimal bronchodilation with minimal side effects. 2 The European Respiratory Society recommends adjusting doses to achieve peak serum levels of 5-15 μg/L. 2

Clinical Context and Positioning

Theophyllines should only be tried in severe COPD patients who remain symptomatic despite combination β2-agonist and anticholinergic bronchodilators, and must be monitored closely for side effects. 2 The British Thoracic Society guidelines emphasize that oral bronchodilators are not usually required in moderate disease. 2

Important Caveats:

• Wide interpatient variability exists in theophylline clearance, causing fourfold differences in dose requirements among similar patients. 1
• Nonlinear elimination may begin at concentrations <10 mcg/mL in some patients, requiring small incremental dose adjustments. 1
• Neonates require special attention: approximately 50% is excreted unchanged in urine (versus 10% in older children/adults), necessitating careful dose reduction and frequent monitoring. 1
• No renal dose adjustment needed in adults and children >3 months of age, as only 10% is excreted unchanged. 1