Gut reaction: impact of systemic diseases on gastrointestinal physiology and drug absorption

Hatton, Grace B.; Madla, Christine M.; Rabbie, Sarit C.; Basit, Abdul W.

doi:10.1016/j.drudis.2018.11.009

Cited by 49 publications

(33 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, diarrhea can occur in many acute gastrointestinal infections (Grover et al, 2008; Albenberg and Wu, 2014), in bowel incontinence (e.g., from muscle or nerve damage), and in chronic conditions such as IBD (Hua et al, 2015). Conversely, constipation is common in IBS and systemic pathologies that affect the endocrine system (e.g., hypothyroidism and diabetes) or central nervous system (e.g., multiple sclerosis and Parkinson’s disease) (Konturek et al, 2011; Hatton et al, 2019). Similarly, drugs that alter gastrointestinal motility can also affect rectal drug delivery (Watts et al, 1992; Brunton et al, 2018).…”

Section: Physiological Factors Influencing Rectal Drug Deliverymentioning

confidence: 99%

Physiological and Pharmaceutical Considerations for Rectal Drug Formulations

Hua

2019

Front. Pharmacol.

137

View full text Add to dashboard Cite

Although the oral route is the most convenient route for drug administration, there are a number of circumstances where this is not possible from either a clinical or pharmaceutical perspective. In these cases, the rectal route may represent a practical alternative and can be used to administer drugs for both local and systemic actions. The environment in the rectum is considered relatively constant and stable and has low enzymatic activity in comparison to other sections of the gastrointestinal tract. In addition, drugs can partially bypass the liver following systemic absorption, which reduces the hepatic first-pass effect. Therefore, rectal drug delivery can provide significant local and systemic levels for various drugs, despite the relatively small surface area of the rectal mucosa. Further development and optimization of rectal drug formulations have led to improvements in drug bioavailability, formulation retention, and drug release kinetics. However, despite the pharmaceutical advances in rectal drug delivery, very few of them have translated to the clinical phase. This review will address the physiological and pharmaceutical considerations influencing rectal drug delivery as well as the conventional and novel drug delivery approaches. The translational challenges and development aspects of novel formulations will also be discussed.

show abstract

Section: Physiological Factors Influencing Rectal Drug Deliverymentioning

confidence: 99%

Physiological and Pharmaceutical Considerations for Rectal Drug Formulations

Hua

2019

Front. Pharmacol.

137

View full text Add to dashboard Cite

show abstract

“…The composition of enterocyte membranes in different animal models [128] could also play a role in different susceptibility to surfactant PEs [9]. It is also worth emphasizing that there can be differences in GI physiology in different disease states [135], which could also influence the action of PEs.…”

Section: Recent Highlightsmentioning

confidence: 99%

Application of Permeation Enhancers in Oral Delivery of Macromolecules: An Update

et al. 2019

View full text Add to dashboard Cite

The application of permeation enhancers (PEs) to improve transport of poorly absorbed active pharmaceutical ingredients across the intestinal epithelium is a widely tested approach. Several hundred compounds have been shown to alter the epithelial barrier, and although the research emphasis has broadened to encompass a role for nanoparticle approaches, PEs represent a key constituent of conventional oral formulations that have progressed to clinical testing. In this review, we highlight promising PEs in early development, summarize the current state of the art, and highlight challenges to the translation of PE-based delivery systems into safe and effective oral dosage forms for patients.

show abstract

“…Over 170 orally-administered drugs are currently known to be substrates for enzymes produced by gut bacteria [21][22][23]. It is therefore important to investigate drugs' susceptibility to microbiota metabolism before formulating for colonic delivery [24,25]. This study will examine the extent to which progesterone, LNG, and MPA may be degraded in the colon, using human fecal slurry.…”

Section: Introductionmentioning

confidence: 99%

Progestogens Are Metabolized by the Gut Microbiota: Implications for Colonic Drug Delivery

et al. 2020

View full text Add to dashboard Cite

Following oral administration, the bioavailability of progestogens is very low and highly variable, in part due to metabolism by cytochrome P450 enzymes found in the mucosa of the small intestine. Conversely, the mucosa in the colon contains much lower levels of cytochrome P450 enzymes, thus, colonic delivery of progestogens may be beneficial. Microbiota in the colon are known to metabolize a great number of drugs, therefore, it is important to understand the stability of these hormones in the presence of colonic flora before developing formulations. The aim of this study was to investigate the stability of three progestogens: progesterone, and its two synthetic analogues, medroxyprogesterone acetate (MPA) and levonorgestrel (LNG), in the presence of human colonic microbiota. Progesterone, MPA, and LNG were incubated in mixed fecal inoculum (simulated human colonic fluid) under anerobic conditions. Progesterone was completely degraded after 2 h, whereas levels of MPA and LNG were still detectable after 24 h. The half-lives of progesterone, MPA, and LNG in fecal inoculum were 28, 644, and 240 min, respectively. This study describes the kinetics of colonic microbial metabolism of these hormones for the first time. MPA and LNG show promise for delivery to the colon, potentially improving pharmacokinetics over current oral delivery methods.

show abstract

Gut reaction: impact of systemic diseases on gastrointestinal physiology and drug absorption

Cited by 49 publications

References 91 publications

Physiological and Pharmaceutical Considerations for Rectal Drug Formulations

Physiological and Pharmaceutical Considerations for Rectal Drug Formulations

Application of Permeation Enhancers in Oral Delivery of Macromolecules: An Update

Progestogens Are Metabolized by the Gut Microbiota: Implications for Colonic Drug Delivery

Contact Info

Product

Resources

About