title: Theophylline absorption and disposition in rabbits: oral, intravenous, and concentration-dependent kinetic studies.
abstract: Theophylline pharmacokinetics following oral and intravenous administration were studied, and the absolute bioavailability of five commercially available products was determined using the rabbit as an in vivo model. Concentration-dependent clearance studies were performed by multiple constant-rate infusion and multiple bolus dose administration of aminophylline. Theophylline pharmacokinetics following the oral administration of these products obeyed the one-compartment open model adequately. However, the data obtained following rapid intravenous aminophylline administration in the rabbit fit either the one-compartment model (half-life = 2.8 hr and the volume of distribution = 4.4 hr and Vd(beta) = 0.708 liter/kg). There were no significant product-to-product differences in the time to peak (tmax), the rate constant of absorption (ka), or the percent of dose absorbed at 1 hr (F1); however, differences in the absolute bioavailability (F), dose-normalized peak serum concentration (Cmax(n)), and percent of dose absorbed at 6 hr (F6) were significant. There was no evidence of concentration-dependent clearance for theophylline in the rabbit in the serum concentration range studied, but the results of the multiple constant-rate infusion study suggest that total clearance decreases at higher serum theophylline concentrations.
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D011817:Rabbits; D013806:Theophylline / Q000008:administration & dosage / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D013806:Theophylline