Theophylline disposition in tetraplegic man.

Abstract

We studied the time-course of serum theophylline concentration after a 30-minute intravenous infusion of aminophylline (6 mg/kg) in 18 traumatic tetraplegic (nine smoking, nine nonsmoking) and in six control (nonsmoking) subjects. All study subjects were healthy men with normal renal function. Pharmacokinetic parameters were calculated from a linear regression analysis of the terminal log-linear portion of the log serum theophylline concentration-time curves. The terminal elimination kinetics of theophylline in this study were best characterized by first order elimination from a one compartment-open model. A statistically significant difference (P less than .05) was demonstrated between the means and variances of theophylline clearance (Cl ml/kg/min) and hours of half-life (t1/2) for control subjects and smoking tetraplegics. Total body clearance of theophylline was greater in all tetraplegic subjects, the greatest difference in total clearance of theophylline adjusted to body weight being observed between tetraplegic smokers and nonsmoking controls with an intact central nervous system (P less than .05). Theophylline volume of distribution (Vdarea) did not differ significantly from Vdarea in able-bodied subjects. Tetraplegic individuals have multiple disorders and marked pharmacokinetic variation, which might be expected to make serum concentration and toxicity of theophylline unpredictable using population averages.