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Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models.
J Pharm Pharmacol. 2016 Dec; 68(12):1501-1515.JP

Abstract

OBJECTIVES

The aim of this study was (1) to determine how closely physiologically based pharmacokinetic (PBPK) models can predict oral bioavailability using a priori knowledge of drug-specific properties and (2) to examine the influence of the biopharmaceutics classification system class on the simulation success.

METHODS

Simcyp Simulator, GastroPlus™ and GI-Sim were used. Compounds with published Biowaiver monographs (bisoprolol (BCS I), nifedipine (BCS II), cimetidine (BCS III), furosemide (BCS IV)) were selected to ensure availability of accurate and reproducible data for all required parameters. Simulation success was evaluated with the average fold error (AFE) and absolute average fold error (AAFE). Parameter sensitivity analysis (PSA) to selected parameters was performed.

KEY FINDINGS

Plasma concentration-time profiles after intravenous administration were forecast within an AAFE < 3. The addition of absorption processes resulted in more variability in the prediction of the plasma profiles, irrespective of biopharmaceutics classification system (BCS) class. The reliability of literature permeability data was identified as a key issue in the accuracy of predicting oral drug absorption.

CONCLUSION

For the four drugs studied, it appears that the forecasting accuracy of the PBPK models is related to the BCS class (BCS I > BCS II, BCS III > BCS IV). These results will need to be verified with additional drugs.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Hansmann S
Institute of Pharmaceutical Technology, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.
Darwich A
Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, UK.
Margolskee A
Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, UK.
Aarons L
Centre for Applied Pharmacokinetic Research, Manchester Pharmacy School, The University of Manchester, Manchester, UK.
Dressman J
Institute of Pharmaceutical Technology, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.

MeSH

Administration, IntravenousAdministration, OralAnimalsBiological AvailabilityBiopharmaceuticsBiotransformationBisoprololCimetidineComputer SimulationDrug CompoundingForecastingFurosemideGastrointestinal AbsorptionHumansModels, BiologicalNifedipinePermeabilityReproducibility of Results

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27781273

Citation

Hansmann, Simone, et al. "Forecasting Oral Absorption Across Biopharmaceutics Classification System Classes With Physiologically Based Pharmacokinetic Models." The Journal of Pharmacy and Pharmacology, vol. 68, no. 12, 2016, pp. 1501-1515.
Hansmann S, Darwich A, Margolskee A, et al. Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models. J Pharm Pharmacol. 2016;68(12):1501-1515.
Hansmann, S., Darwich, A., Margolskee, A., Aarons, L., & Dressman, J. (2016). Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models. The Journal of Pharmacy and Pharmacology, 68(12), 1501-1515. https://doi.org/10.1111/jphp.12618
Hansmann S, et al. Forecasting Oral Absorption Across Biopharmaceutics Classification System Classes With Physiologically Based Pharmacokinetic Models. J Pharm Pharmacol. 2016;68(12):1501-1515. PubMed PMID: 27781273.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models. AU - Hansmann,Simone, AU - Darwich,Adam, AU - Margolskee,Alison, AU - Aarons,Leon, AU - Dressman,Jennifer, Y1 - 2016/10/26/ PY - 2016/06/15/received PY - 2016/07/26/accepted PY - 2016/10/27/pubmed PY - 2017/5/17/medline PY - 2016/10/27/entrez KW - absorption KW - bioavailability KW - biopharmaceutics classification system KW - permeability KW - physiologically based pharmacokinetics SP - 1501 EP - 1515 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 68 IS - 12 N2 - OBJECTIVES: The aim of this study was (1) to determine how closely physiologically based pharmacokinetic (PBPK) models can predict oral bioavailability using a priori knowledge of drug-specific properties and (2) to examine the influence of the biopharmaceutics classification system class on the simulation success. METHODS: Simcyp Simulator, GastroPlus™ and GI-Sim were used. Compounds with published Biowaiver monographs (bisoprolol (BCS I), nifedipine (BCS II), cimetidine (BCS III), furosemide (BCS IV)) were selected to ensure availability of accurate and reproducible data for all required parameters. Simulation success was evaluated with the average fold error (AFE) and absolute average fold error (AAFE). Parameter sensitivity analysis (PSA) to selected parameters was performed. KEY FINDINGS: Plasma concentration-time profiles after intravenous administration were forecast within an AAFE < 3. The addition of absorption processes resulted in more variability in the prediction of the plasma profiles, irrespective of biopharmaceutics classification system (BCS) class. The reliability of literature permeability data was identified as a key issue in the accuracy of predicting oral drug absorption. CONCLUSION: For the four drugs studied, it appears that the forecasting accuracy of the PBPK models is related to the BCS class (BCS I > BCS II, BCS III > BCS IV). These results will need to be verified with additional drugs. SN - 2042-7158 UR - https://www.unboundmedicine.com/medline/citation/27781273/Forecasting_oral_absorption_across_biopharmaceutics_classification_system_classes_with_physiologically_based_pharmacokinetic_models_ DB - PRIME DP - Unbound Medicine ER -