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Modeling the pharmacokinetics of extended release pharmaceutical systems

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Abstract

The pharmacokinetic (PK) models predict the hematic concentration of drugs after the administration. In compartment modeling, the body is described by a set of interconnected “vessels” or “compartments”; the modeling consisting of transient mass balances. Usually the orally administered drugs were considered as immediately available: this cannot describe the administration of extended-release systems. In this work we added to the traditional compartment models the ability to account for a delay in administration, relating this delay to in vitro data. Firstly, the method was validated, applying the model to the dosage of nicotine by chewing-gum; the model was tuned by in vitro/in vivo data of drugs (divalproex-sodium and diltiazem) with medium-rate release kinetics, then it was applied in describing in vivo evolutions due to the assumption of fast- and slow-release systems. The model reveals itself predictive, the same of a Level A in vitro/in vivo correlation, but being physically based, it is preferable to a purely statistical method.

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Abbreviations

ADME:

Adsorption–distribution–metabolism–excretion

AUC:

Area under curve

BCS:

Biopharmaceutics classification system

ER:

Extended release

GI:

Gastro-intestinal tract

IR:

Immediate release

IVIVC:

In vitro/in vivo correlations

MEC:

Minimum effective concentration

MTL:

Minimum toxic level

PBPK:

Physiologically based pharmacokinetics

PK:

Pharmacokinetics

USP:

United States pharmacopoeia

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Authors and Affiliations

  1. Department of Chemical and Food Engineering, University of Salerno, Via Ponte don Melillo, 84084, Fisciano, SA, Italy

    Michela Di Muria, Gaetano Lamberti & Giuseppe Titomanlio

Authors
  1. Michela Di Muria
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  2. Gaetano Lamberti
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  3. Giuseppe Titomanlio
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Correspondence to Gaetano Lamberti.

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Di Muria, M., Lamberti, G. & Titomanlio, G. Modeling the pharmacokinetics of extended release pharmaceutical systems. Heat Mass Transfer 45, 579–589 (2009). https://doi.org/10.1007/s00231-008-0456-7

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  • DOI: https://doi.org/10.1007/s00231-008-0456-7

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