Pharmacokinetics of dyphylline elimination by uremic patients

The elimination kinetics of dyphylline were investigated in four uremic patients receiving chronic hemodialysis treatment. Dyphylline (1000 mg) was administered to each patient orally 2 hr before hemodialysis. Serial arterial and venous blood samples as well as outflowing dialysate samples were collected and analyzed by high-pressure liquid chromatography for dyphylline. The extraction efficiency of the hollow-fiber dialyzers averaged 44.6%. The mean dialysis clearance was 108.7 ml/min which compares favorably to the 57 ml/min metabolic clearance of the drug. A mean of 278.6 mg or 28.34% of the administered dose was recovered in the dialysate during the 4-hr dialysis interval. Half-lives for dyphylline during dialysis ranged from 3.43 to 7.62 hr. The off-dialysis half-lives for two of the four patients studied on a separate occasion were 10.6 and 13.2 hr. The overall clearance calculation projects an average half-life reduction of approximately 65% during hemodialysis. We conclude that dyphylline is dialyzable. Hemodialysis patients receiving dyphylline treatment may require a dosage regimen alteration. In addition, hemodialysis may be useful for the treatment of dyphylline overdose because of its effectiveness in accelerating the removal of the drug.