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

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A Correction to this article was published on 28 September 2021

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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 \( {(AUC)}_0^{\tau } \) and \( {(AUC)}_t^{\infty } \) 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, \( {(AUC)}_0^{\tau } \) or portions of it cannot be used as early exposure rate indicators. \( {(AUC)}_{\tau}^{\infty } \) 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.

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Change history

Abbreviations

BCS:

Biopharmaceutic classification system

PBPK:

Physiologically based pharmacokinetics

PBFTPK:

Physiologically based finite time pharmacokinetics

RMZ:

Remimazolam

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Authors and Affiliations

  1. PharmaInformatics Unit, Research Center ATHENA, Athens, Greece

    Pavlos Chryssafidis, Athanasios A. Tsekouras & Panos Macheras

  2. Faculty of Pharmacy, Laboratory of Biopharmaceutics Pharmacokinetics, National and Kapodistrian University of Athens, Athens, Greece

    Pavlos Chryssafidis & Panos Macheras

  3. Department of Chemistry, Laboratory of Physical Chemistry, National and Kapodistrian University of Athens, Athens, Greece

    Athanasios A. Tsekouras

Authors
  1. Pavlos Chryssafidis
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Correspondence to Panos Macheras.

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Chryssafidis, P., Tsekouras, A.A. & Macheras, P. Revising Pharmacokinetics of Oral Drug Absorption: II Bioavailability-Bioequivalence Considerations. Pharm Res 38, 1345–1356 (2021). https://doi.org/10.1007/s11095-021-03078-w

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