Revising Pharmacokinetics of Oral Drug Absorption: II Bioavailability-Bioequivalence Considerations.

Abstract

To explore the application of the parameters of the physiologically based finite time pharmacokinetic(PBFTPK) models subdivided infirst-order(PBFTPK)1and zero-order (PBFTPK)0models to bioavailability and bioequivalence. To develop a methodology for the estimation of absolute bioavailability, F, from oral data exclusively. Simulated concentration time data were generated from the Bateman equation and compared with data generated from the (PBFTPK)1and (PBFTPK)0models. The blood concentration Cb(τ) at the end of the absorption processτ, 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 forthe (PBFTPK)1and (PBFTPK)0models. An estimate for F was also derived from an areas proportionality using oral data exclusively. The simulated data of the (PBFTPK)0models exhibit rich dynamics encountered in complex drug absorption phenomena. Both (PBFTPK)1and (PBFTPK)0models result either in Cmax= Cb(τ) or Cmax> Cb(τ)for rapidly- and not rapidly-absorbed drugs, respectively; in the latter case, Cb(τ) andτ are meaningful parameters for drug's rate of exposure. For both (PBFTPK)1and (PBFTPK)0models,[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. The (PBFTPK)1and (PBFTPK)0models are more akin to in vivo conditions. Estimates for F can be derived from oral data exclusively.