All disease begins in the gut: Influence of gastrointestinal disorders and surgery on oral drug performance

Abstract

The term "disease" conjures a plethora of graphic imagery for many, and the use of drugs to combat symptoms and treat underlying pathology is at the core of modern medicine. However, the effects of the various gastrointestinal diseases, infections, co-morbidities and the impact of gastrointestinal surgery on the pharmacokinetic and pharmacodynamic behaviour of drugs have been largely overlooked. The better elucidation of disease pathology and the role of underlying cellular and molecular mechanisms have increased our knowledge as far as diagnoses and prognoses are concerned. In addition, the recent advances in our understanding of the intestinal microbiome have linked the composition and function of gut microbiota to disease predisposition and development. This knowledge, however, applies less so in the context of drug absorption and distribution for orally administered dosage forms. Here, we revisit and re-evaluate the influence of a portfolio of gastrointestinal diseases and surgical effects on the functionality of the gastrointestinal tract, their implications for drug delivery and attempt to uncover significant links for clinical practice.

Probiotics and prebiotics in intestinal health and disease: from biology to the clinic

“…14 However, dysbiosis can result from challenges such as medications, infections, ageing, lifestyle, surgery and poor nutrition, 14 , 15 In humans, a range of acute and chronic disorders can be a consequence of perturbation of gut microbial communities. [16][17][18] On a chronic basis, inflammatory bowel disease (IBD), obesity and irritable bowel syndrome (IBS) have all been linked to intestinal bacteria and their activities. 10 This aspect opens up the possibility of influencing the microbiota to reduce disease risk, fortify homeostasis and, in some cases, improve therapeutic status.…”

Direct powder extrusion 3D printing: Fabrication of drug products using a novel single-step process

“…As a sustained release is achieved, the presence of itraconazole in the amorphous phase would enable the enhanced dissolution and absorption of the drug along the gastrointestinal (GI) tract, which is of importance in the distal GI tract regions (i.e. colon) whereby the intestinal fluid volume is lower (Hatton et al, 2018). The observed solubility enhancement is higher than obtained using an alternative technology (nanosuspension technology) with the same HPC grades and similar drug/HPC ratio, which released only about 20% itraconazole (Konnerth et al, 2018).…”

“…This is especially of importance in the distal GI tract regions (i.e. colon), whereby the intestinal fluid volume is reduced (Hatton et al, 2018).…”

Erythromycin and florfenicol treatment of rainbow trout Oncorhynchus mykiss (Walbaum) experimentally infected with Flavobacterium psychrophilum

“…Oral delivery of the medicated diets resulted in 2.9 ppm of FFN and 38 ppm of ERY in fish muscle one day after the last oral treatment (not shown). Antimicrobial tissue concentrations achieved reflect uptake across the intestinal tract (Hatton, Madla, Rabbie, & Basit, ; Hunter & Hirst, ; Lin, Chen, Lin, & Fang, ) and distribution to muscle (Bowser et al, ; Moffitt & Schreck, ; Wang et al, ). Depletion studies of erythromycin A in rainbow trout after oral treatment at 100 mg/kg fish body weight/day for 21 days (Esposito et al, ) revealed a concentration of 0.33 ppm in fish muscle and skin after 10 days.…”