Pharmacokinetics of dyphylline after administration of prodrugs in rabbits and pigs Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/m326m543s

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  • Dyphylline is an analogue of theophylline and the latter is the most popular member of the methyixanthine family in use for the treatment of asthma. Although dyphylline is devoid of some problems associated with theophylline, a reported short half-life for dyphylline (2.1 hours) has made its clinical usefulness limited. In order to avoid these problems a series of prodrugs of dyphylline previously synthesized to liberate dyphylline in a controlled manner after administration was evaluated as a method of drug delivery for dyphylline. Bioavailability comparisons were performed where both 'extent' and 'rate' of absorption were studied. Pharmacokinetic models for description of dyphylline plasma concentrations as delivered by prodrugs were evaluated and used as a basis for data analysis. Numerical deconvolution and a statistical moments method were employed to analyze absorption kinetics. Parameters used to describe this derived absorption profile have better statistical precision than conventional estimates of rate of absorption and provide more information about drug input kinetics. Preliminary experiments in New Zealand White rabbits showed that prolongation of duration of dyphylline blood concentration following oral administration of prodrug suspensions is probably due to slow and prolonged prodrug dissolution in the G-I tract. This characteristic of dyphylline prodrugs may provide a stratagem for design of an effective product. The pig, a carnivorous animal which is comparable with humans in size was chosen as another animal model because the results may give a projectable indication of dyphylline pharmacokinetics following prodrug administration in humans. Experimental data collected indicate that dipivaloyl dyphylline may be a useful approach to deliver dyphylline once the total dosage form has been optimized.
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  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2013-08-05T23:21:21Z (GMT) No. of bitstreams: 1 HuangHuaPin1983.pdf: 2398304 bytes, checksum: 1c5546941d794beb83bd18c36b3c0d0c (MD5)
  • description.provenance : Made available in DSpace on 2013-08-05T23:21:21Z (GMT). No. of bitstreams: 1 HuangHuaPin1983.pdf: 2398304 bytes, checksum: 1c5546941d794beb83bd18c36b3c0d0c (MD5) Previous issue date: 1982-11-12
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2013-08-02T19:25:22Z (GMT) No. of bitstreams: 1 HuangHuaPin1983.pdf: 2398304 bytes, checksum: 1c5546941d794beb83bd18c36b3c0d0c (MD5)
  • description.provenance : Submitted by Kevin Martin (martikev@onid.orst.edu) on 2013-08-02T17:37:16Z No. of bitstreams: 1 HuangHuaPin1983.pdf: 2398304 bytes, checksum: 1c5546941d794beb83bd18c36b3c0d0c (MD5)

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