Investigating the Mechanisms behind the Positive Food Effect of Abiraterone Acetate: In Vitro and Rat In Situ Studies

Braeckmans, Marlies; Augustijns, Patrick; Mols, Raf; Servais, Cécile; Brouwers, Joachim

doi:10.3390/pharmaceutics14050952

Cited by 6 publications

(5 citation statements)

References 13 publications

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“…At a static state of satiety, the concentration of abiraterone in the perfusate was very high, contributing to active absorption. But during digestion, an increased flow of abiraterone was observed compared to fasting, despite its low concentration in the perfusate (22). Thus, at the moment, the mechanisms of the positive food effect are not elucidated.…”

Section: Problems Of Low Bioavailabilitymentioning

confidence: 99%

“…These include low solubility, low solubilization, and unstable food bioavailability. The latter is the subject of a study by Marlies Braeckmans et al (22), who explored the positive food effect of oral abiraterone acetate (commercial name "Zytiga", approved by the Food and Drug Administration (FDA) in 2011). The prodrug is an ester of the abiraterone active compound and is a prime example of a highly lipophilic drug that dissolves better in human intestinal fluids after meals.…”

Section: Problems Of Low Bioavailabilitymentioning

confidence: 99%

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Optimizing Abiraterone Delivery through Intratumoral In Situ Implant: A Prospective Pharmaceutical Development Approach

Bakhrushina,

Buraya,

Moiseev

et al. 2023

sciphar

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Abiraterone acetate is one of the effective therapies in castration-resistant prostate cancer. There is only one dosage form in the form of film-coated tablets. Abiraterone has proven effective but has disadvantages and contraindications that complicate therapy. One of them is a positive food effect affecting the bioavailability and side effects of the drug. Abiraterone is taken strictly on an empty stomach, and the bioavailability of the drug, in this case, reaches only 10%. In addition, the drug is contraindicated in people with hepatic insufficiency since the main metabolism is in the liver. These and other disadvantages can be eliminated by obtaining targeted delivery systems - liposomes and nanocrystals. Another dosage form could be considered for the active pharmaceutical agent that would be cost-effective, accessible and have higher bioavailability for effective treatment. An intratumoral polymeric in situ implant is chosen as an excellent dosage form, the matrix of which will contain an optimized form of abiraterone, which can stably target a tumor.

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Section: Problems Of Low Bioavailabilitymentioning

confidence: 99%

Section: Problems Of Low Bioavailabilitymentioning

confidence: 99%

Optimizing Abiraterone Delivery through Intratumoral In Situ Implant: A Prospective Pharmaceutical Development Approach

Bakhrushina,

Buraya,

Moiseev

et al. 2023

sciphar

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show abstract

“…Recently, Braeckmans et al investigated the mechanism behind the pronounced positive food effect of abiraterone (BCS class IV) [ 111 ]. For this purpose, they conducted both in vitro permeability experiments in the AMI system, i.e., using a regenerated cellulose barrier, in the presence of different biorelevant media and lipids, as well as in situ rat perfusion studies.…”

Section: Lipid-free Membranes For In Vitro Permeability/absorption Pr...mentioning

confidence: 99%

Commercially Available Cell-Free Permeability Tests for Industrial Drug Development: Increased Sustainability through Reduction of In Vivo Studies

et al. 2023

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Replacing in vivo with in vitro studies can increase sustainability in the development of medicines. This principle has already been applied in the biowaiver approach based on the biopharmaceutical classification system, BCS. A biowaiver is a regulatory process in which a drug is approved based on evidence of in vitro equivalence, i.e., a dissolution test, rather than on in vivo bioequivalence. Currently biowaivers can only be granted for highly water-soluble drugs, i.e., BCS class I/III drugs. When evaluating poorly soluble drugs, i.e., BCS class II/IV drugs, in vitro dissolution testing has proved to be inadequate for predicting in vivo drug performance due to the lack of permeability interpretation. The aim of this review was to provide solid proofs that at least two commercially available cell-free in vitro assays, namely, the parallel artificial membrane permeability assay, PAMPA, and the PermeaPad® assay, PermeaPad, in different formats and set-ups, have the potential to reduce and replace in vivo testing to some extent, thus increasing sustainability in drug development. Based on the literature review presented here, we suggest that these assays should be implemented as alternatives to (1) more energy-intense in vitro methods, e.g., refining/replacing cell-based permeability assays, and (2) in vivo studies, e.g., reducing the number of pharmacokinetic studies conducted on animals and humans. For this to happen, a new and modern legislative framework for drug approval is required.

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“…The SPIP model is very versatile, as it enables mechanistic investigations of drug permeability at defined luminal conditions. This includes the effect of, for instance, the luminal drug concentration [133], pH [134], perfusion rate [135], fasted and fed conditions [136], formulation and excipients effects [137] and regional intestinal differences [138]. It also has the advantage of maintained physiological regulation of gut functions, including intact neurohormonal and immunological feedback mechanisms, which opens up the possibility of evaluating drug permeability at different physiological and pathophysiological states [139].…”

Section: Single-pass Intestinal Perfusionmentioning

confidence: 99%

Challenges in Permeability Assessment for Oral Drug Product Development

Koziolek,

Augustijns,

Berger

et al. 2023

Pharmaceutics

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Drug permeation across the intestinal epithelium is a prerequisite for successful oral drug delivery. The increased interest in oral administration of peptides, as well as poorly soluble and poorly permeable compounds such as drugs for targeted protein degradation, have made permeability a key parameter in oral drug product development. This review describes the various in vitro, in silico and in vivo methodologies that are applied to determine drug permeability in the human gastrointestinal tract and identifies how they are applied in the different stages of drug development. The various methods used to predict, estimate or measure permeability values, ranging from in silico and in vitro methods all the way to studies in animals and humans, are discussed with regard to their advantages, limitations and applications. A special focus is put on novel techniques such as computational approaches, gut-on-chip models and human tissue-based models, where significant progress has been made in the last few years. In addition, the impact of permeability estimations on PK predictions in PBPK modeling, the degree to which excipients can affect drug permeability in clinical studies and the requirements for colonic drug absorption are addressed.

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Investigating the Mechanisms behind the Positive Food Effect of Abiraterone Acetate: In Vitro and Rat In Situ Studies

Cited by 6 publications

References 13 publications

Optimizing Abiraterone Delivery through Intratumoral In Situ Implant: A Prospective Pharmaceutical Development Approach

Optimizing Abiraterone Delivery through Intratumoral In Situ Implant: A Prospective Pharmaceutical Development Approach

Commercially Available Cell-Free Permeability Tests for Industrial Drug Development: Increased Sustainability through Reduction of In Vivo Studies

Challenges in Permeability Assessment for Oral Drug Product Development

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