Effect of probenecid on dyphylline elimination

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Abstract
Dyphylline is a methylxanthine bronchodilator with such a short biologic t1/2 [half-life] that development of practical dosing regimens is difficult. Because its rapid renal elimination suggests active secretion, the effect of 1 g probenecid on single-dose elimination kinetics of dyphylline was determined. Twelve subjects (6 male) participated in a crossover design. Subjects were their own controls and received dyphylline, 20 mg/kg orally, alone and after probenecid. The dyphylline t1/2 increased from 2.57 .+-. 0.45 to 4.88 .+-. 1.2 h, whereas the elimination rate constant decreased from 0.276 .+-. 0.056 to 0.150 .+-. 0.037 h-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 per h. 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.