Pavlos Chryssafidis1,2, Athanasios A Tsekouras1,3, Panos Macheras4,5. 1. PharmaInformatics Unit, Research Center ATHENA, Athens, Greece. 2. Faculty of Pharmacy, Laboratory of Biopharmaceutics Pharmacokinetics, National and Kapodistrian University of Athens, Athens, Greece. 3. Department of Chemistry, Laboratory of Physical Chemistry, National and Kapodistrian University of Athens, Athens, Greece. 4. PharmaInformatics Unit, Research Center ATHENA, Athens, Greece. macheras@pharm.uoa.gr. 5. Faculty of Pharmacy, Laboratory of Biopharmaceutics Pharmacokinetics, National and Kapodistrian University of Athens, Athens, Greece. macheras@pharm.uoa.gr.
Abstract
PURPOSE: To explore the application of the parameters of the physiologically based finite time pharmacokinetic (PBFTPK) models subdivided in first-order (PBFTPK)1 and zero-order (PBFTPK)0 models to bioavailability and bioequivalence. To develop a methodology for the estimation of absolute bioavailability, F, from oral data exclusively. METHODS: Simulated concentration time data were generated from the Bateman equation and compared with data generated from the (PBFTPK)1 and (PBFTPK)0 models. The blood concentration Cb(τ) at the end of the absorption process τ, was compared to Cmax; the utility of [Formula: see text] and [Formula: see text] in bioequivalence assessment was also explored. Equations for the calculation of F from oral data were derived for the (PBFTPK)1 and (PBFTPK)0 models. An estimate for F was also derived from an areas proportionality using oral data exclusively. RESULTS: The simulated data of the (PBFTPK)0 models exhibit rich dynamics encountered in complex drug absorption phenomena. Both (PBFTPK)1 and (PBFTPK)0 models result either in Cmax = Cb(τ) or Cmax > Cb(τ) for rapidly- and not rapidly-absorbed drugs, respectively; in the latter case, Cb(τ) and τ are meaningful parameters for drug's rate of exposure. For both (PBFTPK)1 and (PBFTPK)0 models, [Formula: see text] or portions of it cannot be used as early exposure rate indicators. [Formula: see text] is a useful parameter for the assessment of extent of absorption for very rapidly absorbed drugs. An estimate for F for theophylline formulations was found close to unity. CONCLUSION: The (PBFTPK)1 and (PBFTPK)0 models are more akin to in vivo conditions. Estimates for F can be derived from oral data exclusively.
PURPOSE: To explore the application of the parameters of the physiologically based finite time pharmacokinetic (PBFTPK) models subdivided in first-order (PBFTPK)1 and zero-order (PBFTPK)0 models to bioavailability and bioequivalence. To develop a methodology for the estimation of absolute bioavailability, F, from oral data exclusively. METHODS: Simulated concentration time data were generated from the Bateman equation and compared with data generated from the (PBFTPK)1 and (PBFTPK)0 models. The blood concentration Cb(τ) at the end of the absorption process τ, was compared to Cmax; the utility of [Formula: see text] and [Formula: see text] in bioequivalence assessment was also explored. Equations for the calculation of F from oral data were derived for the (PBFTPK)1 and (PBFTPK)0 models. An estimate for F was also derived from an areas proportionality using oral data exclusively. RESULTS: The simulated data of the (PBFTPK)0 models exhibit rich dynamics encountered in complex drug absorption phenomena. Both (PBFTPK)1 and (PBFTPK)0 models result either in Cmax = Cb(τ) or Cmax > Cb(τ) for rapidly- and not rapidly-absorbed drugs, respectively; in the latter case, Cb(τ) and τ are meaningful parameters for drug's rate of exposure. For both (PBFTPK)1 and (PBFTPK)0 models, [Formula: see text] or portions of it cannot be used as early exposure rate indicators. [Formula: see text] is a useful parameter for the assessment of extent of absorption for very rapidly absorbed drugs. An estimate for F for theophylline formulations was found close to unity. CONCLUSION: The (PBFTPK)1 and (PBFTPK)0 models are more akin to in vivo conditions. Estimates for F can be derived from oral data exclusively.
Keywords:
Bioavailability; bioequivalence; finite time of absorption; physiologically based finite time pharmacokinetic models; physiologically based pharmacokinetic models
Authors: Jonathan Brown; Caly Chien; Peter Timmins; Andrew Dennis; Walter Doll; Erik Sandefer; Richard Page; Richard E Nettles; Li Zhu; Dennis Grasela Journal: J Pharm Sci Date: 2013-04-05 Impact factor: 3.534
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