Graduate Thesis Or Dissertation
 

Bioavailability and pharmacokinetics of dyphylline and theophylline in rabbits

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/xk81jp883

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  • The bioavailability and pharmacokinetics of theophylline in rabbits were determined following both oral and intravenous administration of the drug. Serum theophylline concentrations were determined using high pressure liquid chromatography. Pharmacokinetic parameters were determined and verified by computer analysis. The overall mean Beta disposition constant was 0.089 hr⁻¹ which corresponds to a total body half-life of 7.79 hours. Results are compared with previously published results in humans. In vitro dissolution studies of a prolonged release product showed rapid dissolution in simulated intestinal fluid and very poor dissolution in simulated gastric fluid. The same product was completely absorbed in rabbits. Rabbits are shown to be useful experimental animals for testing bioavailability of orally administered theophylline. Pharmacokinetic parameters obtained in rabbits correlate well with those reported in humans. Part II. Dyphylline Rabbits were administered intravenous dyphylline and commercially available dyphylline tablets. Serum dyphylline concentrations were determined using high pressure liquid chromatography. Computer analysis of serum concentrations determined pharmacokinetic parameters. Total body elimination half-life of dyphylline in rabbits was 3.89 hours. Published data for dyphylline studies in humans were analyzed by computer fitting the reported serum concentration data and compared to values obtained in this study. Computer analysis and linear regression showed that the reported elimination half-life of dyphylline in humans may be an underestimate of the true value. Multiple dosing studies in rabbits showed a poor correlation of values obtained in this study with computer predicted values. The loss of hematocrit due to frequent blood sampling is offered as a possible explanation. It is proposed that dyphylline enters or binds to erythrocytes similar to theophylline. Thus the decreased hematocrit should allow for a larger serum concentration value than predicted as was seen in this study. In vitro dissolution and in vivo availability studies showed that the dyphylline tablets studied were rapidly dissolved, rapidly absorbed, and completely available. Rabbits are shown to be useful experimental animals for bioavailability and pharmacokinetic studies involving dyphylline.
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