Theophylline disposition in tetraplegic man

Area of Science:

• Pharmacokinetics
• Clinical Pharmacology
• Neuroscience

Background:

• Traumatic tetraplegia can alter drug metabolism and elimination.
• Understanding theophylline pharmacokinetics in tetraplegic patients is crucial for safe and effective dosing.
• Smoking status may influence drug clearance in individuals with spinal cord injuries.

Purpose of the Study:

• To investigate the time-course of serum theophylline concentration in traumatic tetraplegic subjects.
• To compare theophylline pharmacokinetic parameters between smoking and nonsmoking tetraplegics and healthy controls.
• To assess the impact of tetraplegia and smoking on theophylline clearance and half-life.

Main Methods:

• Intravenous infusion of aminophylline (6 mg/kg) over 30 minutes in 18 tetraplegic (9 smoking, 9 nonsmoking) and 6 control subjects.
• Serum theophylline concentrations were measured over time.
• Pharmacokinetic parameters, including clearance (Cl) and half-life (t1/2), were calculated using linear regression analysis of log-transformed data, best fitting a one-compartment open model.

Main Results:

• A statistically significant difference (P < .05) in theophylline clearance and half-life was observed between control subjects and smoking tetraplegics.
• Total body clearance of theophylline was significantly greater in all tetraplegic subjects compared to controls.
• The greatest difference in theophylline clearance adjusted to body weight was between tetraplegic smokers and nonsmoking controls (P < .05).

Conclusions:

• Tetraplegic individuals, particularly smokers, exhibit altered theophylline clearance and half-life compared to able-bodied controls.
• Theophylline volume of distribution (Vdarea) was not significantly different between groups.
• Marked pharmacokinetic variation in tetraplegic individuals necessitates individualized dosing to avoid unpredictable serum concentrations and potential toxicity.