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Prediction of food effects on the absorption of celecoxib based on biorelevant dissolution testing coupled with physiologically based pharmacokinetic modeling.
Eur J Pharm Biopharm. 2009 Sep; 73(1):107-14.EJ

Abstract

Since the rate-determining step to the intestinal absorption of poorly soluble drugs is the dissolution in the gastrointestinal (GI) tract, postprandial changes in GI physiology, in addition to any specific interactions between drug and food, are expected to affect the pharmacokinetics and bioavailability of such drugs. In this study, in vitro dissolution testing using biorelevant media coupled with in silico physiologically based pharmacokinetic (PBPK) modeling was applied to the prediction of food effects on the absorption of a poorly soluble drug, celecoxib, from 200mg capsules. A PBPK model was developed based on STELLA software using dissolution kinetics, solubility, standard GI parameters and post-absorptive disposition parameters. Solubility, dissolution profiles and initial dissolution rate from celecoxib 200mg capsules were measured in biorelevant and compendial media. Standard GI parameters (gastric emptying rate and fluid volume) were varied according to the dosing conditions. Disposition parameters were estimated by fitting compartmental models to the oral PK data, since intravenous data are not available for celecoxib. Predictions of food effects and average plasma profiles were evaluated using the AUC and C(max) and the difference factor (f(1)). An approximately 7-fold difference in the maximum percentage dissolved was observed in in vitro dissolution tests designed to represent the fed and fasted states. By contrast, the food effect estimated by simulating the plasma profiles with the PBPK model predicted only a slight delay in the peak plasma level (approximately 1h), and modest increases in the C(max) and AUC of approximately 1.9-fold and 1.3-fold in the fed state, respectively. The PBPK approach, combining in silico simulation coupled with biorelevant dissolution test results, thus corresponds much better to the food effect observed for celecoxib in vivo. Additionally, point estimates of AUC and C(max) as well as f(1) calculations demonstrated clear advantages of using results in biorelevant rather than compendial media in the PBPK model.

Authors+Show Affiliations

Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

19465123

Citation

Shono, Yasushi, et al. "Prediction of Food Effects On the Absorption of Celecoxib Based On Biorelevant Dissolution Testing Coupled With Physiologically Based Pharmacokinetic Modeling." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 73, no. 1, 2009, pp. 107-14.
Shono Y, Jantratid E, Janssen N, et al. Prediction of food effects on the absorption of celecoxib based on biorelevant dissolution testing coupled with physiologically based pharmacokinetic modeling. Eur J Pharm Biopharm. 2009;73(1):107-14.
Shono, Y., Jantratid, E., Janssen, N., Kesisoglou, F., Mao, Y., Vertzoni, M., Reppas, C., & Dressman, J. B. (2009). Prediction of food effects on the absorption of celecoxib based on biorelevant dissolution testing coupled with physiologically based pharmacokinetic modeling. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 73(1), 107-14. https://doi.org/10.1016/j.ejpb.2009.05.009
Shono Y, et al. Prediction of Food Effects On the Absorption of Celecoxib Based On Biorelevant Dissolution Testing Coupled With Physiologically Based Pharmacokinetic Modeling. Eur J Pharm Biopharm. 2009;73(1):107-14. PubMed PMID: 19465123.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prediction of food effects on the absorption of celecoxib based on biorelevant dissolution testing coupled with physiologically based pharmacokinetic modeling. AU - Shono,Yasushi, AU - Jantratid,Ekarat, AU - Janssen,Niels, AU - Kesisoglou,Filippos, AU - Mao,Yun, AU - Vertzoni,Maria, AU - Reppas,Christos, AU - Dressman,Jennifer B, Y1 - 2009/05/22/ PY - 2009/03/19/received PY - 2009/05/11/revised PY - 2009/05/17/accepted PY - 2009/5/26/entrez PY - 2009/5/26/pubmed PY - 2010/4/20/medline SP - 107 EP - 14 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 73 IS - 1 N2 - Since the rate-determining step to the intestinal absorption of poorly soluble drugs is the dissolution in the gastrointestinal (GI) tract, postprandial changes in GI physiology, in addition to any specific interactions between drug and food, are expected to affect the pharmacokinetics and bioavailability of such drugs. In this study, in vitro dissolution testing using biorelevant media coupled with in silico physiologically based pharmacokinetic (PBPK) modeling was applied to the prediction of food effects on the absorption of a poorly soluble drug, celecoxib, from 200mg capsules. A PBPK model was developed based on STELLA software using dissolution kinetics, solubility, standard GI parameters and post-absorptive disposition parameters. Solubility, dissolution profiles and initial dissolution rate from celecoxib 200mg capsules were measured in biorelevant and compendial media. Standard GI parameters (gastric emptying rate and fluid volume) were varied according to the dosing conditions. Disposition parameters were estimated by fitting compartmental models to the oral PK data, since intravenous data are not available for celecoxib. Predictions of food effects and average plasma profiles were evaluated using the AUC and C(max) and the difference factor (f(1)). An approximately 7-fold difference in the maximum percentage dissolved was observed in in vitro dissolution tests designed to represent the fed and fasted states. By contrast, the food effect estimated by simulating the plasma profiles with the PBPK model predicted only a slight delay in the peak plasma level (approximately 1h), and modest increases in the C(max) and AUC of approximately 1.9-fold and 1.3-fold in the fed state, respectively. The PBPK approach, combining in silico simulation coupled with biorelevant dissolution test results, thus corresponds much better to the food effect observed for celecoxib in vivo. Additionally, point estimates of AUC and C(max) as well as f(1) calculations demonstrated clear advantages of using results in biorelevant rather than compendial media in the PBPK model. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/19465123/Prediction_of_food_effects_on_the_absorption_of_celecoxib_based_on_biorelevant_dissolution_testing_coupled_with_physiologically_based_pharmacokinetic_modeling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(09)00159-3 DB - PRIME DP - Unbound Medicine ER -