What is the appropriate dose of aminophylline for a smoker?

Aminophylline Dosing for Smokers

For smokers requiring aminophylline infusion, increase the maintenance infusion rate to approximately 0.9-1.0 mg/kg/hr (compared to 0.7 mg/kg/hr in non-smokers) due to significantly enhanced theophylline clearance caused by smoking-induced hepatic enzyme induction.

Pharmacokinetic Impact of Smoking

Smoking substantially alters theophylline metabolism through hepatic enzyme induction:

• Smokers demonstrate 40-50% higher theophylline clearance compared to non-smokers (0.051 vs 0.035 L/kg/hr), requiring proportionally higher maintenance doses to achieve therapeutic serum concentrations 1, 2
• The enhanced clearance persists in smokers regardless of the route or formulation of theophylline administered 1
• This effect is mediated through polycyclic hydrocarbon-inducible microsomal drug-metabolizing enzymes 1

Recommended Dosing Strategy

Loading Dose

• Administer standard loading dose of 4.6 mg/kg theophylline (5.7 mg/kg as aminophylline) over 30 minutes, as smoking status does not significantly affect volume of distribution 3, 1
• Each mg/kg administered produces approximately 2 mcg/mL increase in serum concentration 3
• Target post-loading serum concentration of 10 mcg/mL 3

Maintenance Infusion

• For smokers: initiate infusion at 0.8-1.0 mg/kg/hr (as aminophylline) rather than the standard 0.5 mg/kg/hr used in non-smoking adults 3, 2
• The 0.7 mg/kg/hr dose mentioned in your question is insufficient for most smokers and will likely result in subtherapeutic levels 2

Critical Monitoring Requirements

Obtain serum theophylline concentration at these specific timepoints:

• 30 minutes post-loading dose to confirm appropriate initial level and guide further loading if needed 3
• One expected half-life after starting infusion (approximately 4-6 hours in smokers due to enhanced clearance) to detect accumulation or declining levels 3
• 12-24 hours after infusion initiation for dose adjustment 3
• Every 24 hours thereafter until stable therapeutic range achieved 3

Target Therapeutic Range

• Maintain serum concentrations between 10-20 mcg/mL 3, 4
• Levels >20 mcg/mL indicate toxicity risk 4

Common Pitfalls to Avoid

Do not assume standard dosing applies to smokers:

• The widely cited 0.9 mg/kg/hr dosage is based on non-smoking populations and represents 40% less than actual clearance in acutely ill patients 2
• Smokers given standard non-smoker doses will consistently achieve subtherapeutic levels 1, 2

Account for clinical factors that may counteract smoking's effect:

• Congestive heart failure, pneumonia, or severe airway obstruction significantly decrease clearance and may offset smoking-induced increases 2
• In smokers with these conditions, start at 0.5-0.7 mg/kg/hr and titrate based on levels 2

Verify recent theophylline use:

• If patient took theophylline within 12 hours (short-acting) or 24 hours (sustained-release), obtain pre-load serum level before any aminophylline administration 4, 5
• Half-dose loading (3 mg/kg) in this scenario carries 23% risk of toxic levels 4

Dose Calculation Method

Use ideal body weight for all calculations, as theophylline distributes poorly into body fat 3:

• Loading dose produces similar variability whether calculated on total or ideal body weight 4
• Mean change per mg/kg is 1.58 mcg/mL when using ideal body weight 4

Clinical Context Considerations

The evidence does not support routine aminophylline use in COPD exacerbations:

• A randomized controlled trial found no clinically important benefit when aminophylline (0.5 mg/kg/hr) was added to bronchodilators and corticosteroids in non-acidotic COPD exacerbations 6
• Nausea occurred in 46% of aminophylline-treated patients versus 22% with placebo 6
• Reserve aminophylline for specific indications (severe refractory bronchospasm, cardiac applications) rather than routine use 6