Pharmacokinetics - based comparison among certain enhanced elimination procedures used in treatment of theophylline toxicity

ABSTRACT

Thirty patients with theophylline overdose were selected to study the pharmacokinetics of theophylline during continuous hemodialysis with and without filtration, charcoal hemoperfusion and intestinal dialysis using multiple-dose activated charcoal [MDAC]. Patients were classified into three equal groups; each comprised 10 patients. Group-1 started the enhanced elimination by continuous hemodialysis with filtration, Group-2 by charcoal hemoperfusion and Group-3 by continuous hemodialysis alone. The extracorporeal procedures in the three groups were initiated 2 hours post-admission and terminated when patient's vomiting had settled where MDAC was started. Serum theophylline concentrations peaked at 2 hours, for both hemofiltration and hemoperfusion groups, which is the time of initiating the extracorporeal procedures. For hemodialysis group, drug concentration peaked at 3 hours [1 hour post-initiating hemodialysis]. Following the peak, serum levels of patients in hemofiltration group showed significant greater decrease compared with patients in either charcoal hemoperfusion or hemodialysis groups. Also, charcoal hemoperfusion produced the same effects compared with hemodialysis alone. With respect to the pharmacokinetic parameters, there was a significant shorter half-life and a greater clearance for theophylline as a result of continuous hemodialysis with filtration [1.27 +/- 0.214 hours and 0.273 +/- 0.046 L/h/kg, respectively] versus charcoal hemoperfusion [1.86 +/- 0.335 hours and 0.186 +/- 0.034 Mg, respectively], continuous hemodialysis [3.73 +/- 1.087 hours and 0.093 +/- 0.031 L/h/kg, respectively] or gastrointestinal dialysis by MDAC [5.58 +/- 1.36 hours and 0.0621 +/- 0.0163 L/h/kg, respectively]. In conclusion, immediate continuous dialysis with filtration is an effective, rapid, and safe treatment of the life-threatening toxicity of theophyiline overdose. In combination with oral activated charcoal, hemofiltration is considered as a realistic and practical alternative to charcoal hemoperfusion