Drug Absorption V: Influence of Food on Oral Absorption of Phenobarbital in Rats

1971 ◽  
Vol 60 (11) ◽  
pp. 1639-1641 ◽  
Author(s):  
S. Kojima ◽  
R.B. Smith ◽  
J.T. Doluisio
Keyword(s):  
Drug Absorption ◽  
Oral Absorption ◽  
Influence Of Food

A physiologically based biopharmaceutical analysis of zolpidem

2021 ◽  
Author(s):  
◽  
Rafael Leal Monteiro Paraiso
Keyword(s):  
Drug Development ◽  
Drug Absorption ◽  
Oral Absorption ◽  
Food Effect ◽  
Simulation Software ◽  
Oral Drug ◽  
Oral Drug Absorption ◽  
Physiologically Based

Computational oral absorption models, in particular PBBM models, provide a powerful tool for researchers and pharmaceutical scientists in drug discovery and formulation development, as they mimic and can describe the physiologically processes relevant to the oral absorption. PBBM models provide in vivo context to in vitro data experiments and allow for a dynamic understanding of in vivo drug disposition that is not typically provided by data from standard in vitro assays. Investigations using these models permit informed decision-making, especially regarding to formulation strategies in drug development. PBBM models, but can also be used to investigate and provide insight into mechanisms responsible for complex phenomena such as food effect in drug absorption. Although there are obviously still some gaps regarding the in silico construction of the gastrointestinal environment, ongoing research in the area of oral drug absorption (e.g. the UNGAP, AGE-POP and InPharma projects) will increase knowledge and enable improvement of these models. PBBM can nowadays provide an alternative approach to the development of in vitro–in vivo correlations. The case studies presented in this thesis demonstrate how PBBM can address a mechanistic understanding of the negative food effect and be used to set clinically relevant dissolution specification for zolpidem immediate release tablets. In both cases, we demonstrated the importance of integrating drug properties with physiological variables to mechanistically understand and observe the impact of these parameters on oral drug absorption. Various complex physiological processes are initiated upon food consumption, which can enhance or reduce a drug’s dissolution, solubility, and permeability and thus lead to changes in drug absorption. With improvements in modeling and simulation software and design of in vitro studies, PBBM modeling of food effects may eventually serve as a surrogate for clinical food effect studies for new doses and formulations or drugs. Furthermore, the application of these models may be even more critical in case of compounds where execution of clinical studies in healthy volunteers would be difficult (e.g., oncology drugs). In the fourth chapter we have demonstrated the establishment of the link between biopredictive in vitro dissolution testing (QC or biorelevant method) PBBM coupled with PD modeling opens the opportunity to set truly clinically relevant specifications for drug release. This approach can be extended to other drugs regardless of its classification according to the BCS. With the increased adoption of PBBM, we expect that best practices in development and verification of these models will be established that can eventually inform a regulatory guidance. Therefore, the application of Physiologically Based Biopharmaceutical Modelling is an area with great potential to streamline late-stage drug development and impact on regulatory approval procedures. Freie Schlagwörter / Tags

Expression, regulation and function of intestinal drug transporters: an update

2017 ◽  
Vol 398 (2) ◽  
pp. 175-192 ◽  
Author(s):  
Janett Müller ◽  
Markus Keiser ◽  
Marek Drozdzik ◽  
Stefan Oswald
Keyword(s):  
Drug Absorption ◽  
Drug Transport ◽  
Drug Exposure ◽  
Oral Absorption ◽  
Basolateral Membrane ◽  
Oral Drug ◽  
Human Intestine ◽  
Intestinal Drug Absorption ◽  
Intestinal Transporters ◽  
And Function

Abstract Although oral drug administration is currently the favorable route of administration, intestinal drug absorption is challenged by several highly variable and poorly predictable processes such as gastrointestinal motility, intestinal drug solubility and intestinal metabolism. One further determinant identified and characterized during the last two decades is the intestinal drug transport that is mediated by several transmembrane proteins such as P-gp, BCRP, PEPT1 and OATP2B1. It is well-established that intestinal transporters can affect oral absorption of many drugs in a significant manner either by facilitating their cellular uptake or by pumping them back to gut lumen, which limits their oral bioavailability. Their functional relevance becomes even more apparent in cases of unwanted drug-drug interactions when concomitantly given drugs that cause transporter induction or inhibition, which in turn leads to increased or decreased drug exposure. The longitudinal expression of several intestinal transporters is not homogeneous along the human intestine, which may have functional implications on the preferable site of intestinal drug absorption. Besides the knowledge about the expression of pharmacologically relevant transporters in human intestinal tissue, their exact localization on the apical or basolateral membrane of enterocytes is also of interest but in several cases debatable. Finally, there is obviously a coordinative interplay of intestinal transporters (apical–basolateral), intestinal enzymes and transporters as well as intestinal and hepatic transporters. This review aims to give an updated overview about the expression, localization, regulation and function of clinically relevant transporter proteins in the human intestine.

The Influence of Food on the Oral Absorption of Bevantolol

1987 ◽  
Vol 27 (4) ◽  
pp. 297-299 ◽  
Author(s):  
Roger D. Toothaker ◽  
Edward J. Randinitis ◽  
Cynthia Nelson ◽  
Arlyn W. Kinkel PhD ◽  
J. Richard Goulet
Keyword(s):  
Oral Absorption ◽  
Influence Of Food

Influence of Food on the Oral Absorption and Bioavailability of Moricizine

1991 ◽  
Vol 31 (9) ◽  
pp. 792-795 ◽  
Author(s):  
Henry J. Pieniaszek ◽  
Dariel C. Rakestraw ◽  
William L. Schary ◽  
Roger L. Williams
Keyword(s):  
Oral Absorption ◽  
Influence Of Food

scholarly journals Characterization of P-Glycoprotein Inhibitors for Evaluating the Effect of P-Glycoprotein on the Intestinal Absorption of Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 388
Author(s):  
Yusuke Kono ◽  
Iichiro Kawahara ◽  
Kohei Shinozaki ◽  
Ikuo Nomura ◽  
Honoka Marutani ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Drug Absorption ◽  
Absorption Rate ◽  
Oral Absorption ◽  
Cancer Resistance ◽  
Wild Type ◽  
Glycoprotein P ◽  
Cell Monolayers ◽  
P Glycoprotein ◽  
New Chemical Entities

For developing oral drugs, it is necessary to predict the oral absorption of new chemical entities accurately. However, it is difficult because of the involvement of efflux transporters, including P-glycoprotein (P-gp), in their absorption process. In this study, we conducted a comparative analysis on the inhibitory activities of seven P-gp inhibitors (cyclosporin A, GF120918, LY335979, XR9576, WK-X-34, VX-710, and OC144-093) to evaluate the effect of P-gp on drug absorption. GF120918, LY335979, and XR9576 significantly decreased the basal-to-apical transport of paclitaxel, a P-gp substrate, across Caco-2 cell monolayers. GF120918 also inhibited the basal-to-apical transport of mitoxantrone, a breast cancer resistance protein (BCRP) substrate, in Caco-2 cells, whereas LY335979 hardly affected the mitoxantrone transport. In addition, the absorption rate of paclitaxel after oral administration in wild-type mice was significantly increased by pretreatment with LY335979, and it was similar to that in mdr1a/1b knockout mice. Moreover, the absorption rate of topotecan, a BCRP substrate, in wild-type mice pretreated with LY335979 was similar to that in mdr1a/1b knockout mice but significantly lower than that in bcrp knockout mice. These results indicate that LY335979 has a selective inhibitory activity for P-gp, and would be useful for evaluating the contribution of P-gp to drug absorption.

scholarly journals In-Depth Characterization of EpiIntestinal Microtissue as a Model for Intestinal Drug Absorption and Metabolism in Human

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 405 ◽  
Author(s):  
Yunhai Cui ◽  
Stephanie Claus ◽  
David Schnell ◽  
Frank Runge ◽  
Caroline MacLean
Keyword(s):  
Drug Absorption ◽  
Oral Absorption ◽  
Human Intestine ◽  
Cancer Resistance ◽  
Holistic Model ◽  
Glycoprotein P ◽  
Intestinal Drug Absorption ◽  
Fraction Absorbed ◽  
Vitro Model

The Caco-2 model is a well-accepted in vitro model for the estimation of fraction absorbed in human intestine. Due to the lack of cytochrome P450 3A4 (CYP3A4) activities, Caco-2 model is not suitable for the investigation of intestinal first-pass metabolism. The purpose of this study is to evaluate a new human intestine model, EpiIntestinal microtissues, as a tool for the prediction of oral absorption and metabolism of drugs in human intestine. The activities of relevant drug transporters and drug metabolizing enzymes, including MDR1 P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), CYP3A4, CYP2J2, UDP-glucuronosyltransferases (UGT), carboxylesterases (CES), etc., were detected in functional assays with selective substrates and inhibitors. Compared to Caco-2, EpiIntestinal microtissues proved to be a more holistic model for the investigation of drug absorption and metabolism in human gastrointestinal tract.

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