Effect of probenecid on dyphylline elimination

Dyphylline is a methylxanthine bronchodilator with such a short a biologic t 1/2 that development of practical dosing regimens has been difficult. Because its rapid renal elimination suggests active secretion, the effect of 1 gm probenecid on single-dose elimination kinetics of dyphylline was determined. Twelve subjects (six male, six female) participated in a crossover design. Subjects were their own controls and received dyphylline, 20 mg/kg orally, alone and after probenecid. The dyphylline t 1/2 increased from 2.57 +/- 0.45 to 4.88 +/- 1.2 hr, whereas the elimination rate constant decreased from 0.276 +/- 0.056 to 0.150 +/- 0.037 hr-1 after probenecid. There was no significant change in the dyphylline apparent volume of distribution. Dyphylline total body clearance fell from 173 +/- 20 to 95 +/- 12 ml/kg . hr. The combined use of these drugs may lead to a practical dyphylline dosage schedule in aminophylline-hypersensitive patients or those incapacitated by theophylline gastrointestinal side effects.