Effect of probenecid on dyphylline elimination

Area of Science:

• Pharmacology
• Clinical Pharmacology

Background:

• Dyphylline, a methylxanthine bronchodilator, has a short biologic half-life (t 1/2) complicating dosing.
• Rapid renal elimination suggests active secretion of dyphylline.

Purpose of the Study:

• To determine the effect of probenecid on dyphylline elimination kinetics.
• To explore potential for improved dyphylline dosing regimens.

Main Methods:

• A crossover study involving 12 subjects (6 male, 6 female).
• Subjects received dyphylline (20 mg/kg orally) alone and after 1 gm of probenecid.
• Dyphylline elimination kinetics, including t 1/2 and clearance, were measured.

Main Results:

• Probenecid increased dyphylline's t 1/2 from 2.57 to 4.88 hours.
• Elimination rate constant decreased from 0.276 to 0.150 hr-1.
• Total body clearance of dyphylline significantly decreased from 173 to 95 ml/kg/hr.

Conclusions:

• Probenecid inhibits dyphylline's renal elimination, likely via active secretion blockade.
• Combined use may enable practical dyphylline dosage schedules.
• This could benefit patients with aminophylline hypersensitivity or theophylline-induced gastrointestinal issues.