The colon targeting efficacies of mesalazine medications and their impacts on the gut microbiome.

Successful treatment of ulcerative colitis (UC) is highly dependent on several parameters, including dosing regimen and the ability to deliver drugs to the disease site. In this study two strategies for delivering mesalazine (5-aminosalicylic acid, 5-ASA) to the colon were compared in an advanced in vitro model of the human gastrointestinal (GI) tract, the SHIME® system. Herein, a prodrug strategy employing bacteria-mediated drug release (sulfasalazine, Azulfidine®) was evaluated alongside a formulation strategy that utilised pH and bacteria-mediated release (5-ASA, Octasa® 1600 mg). SHIME® experiments were performed simulating both the GI physiology and colonic microbiota under healthy and inflammatory bowel disease (IBD) conditions, to study the impact of the disease state and ileal pH variability on colonic 5-ASA delivery. In addition, the effects of the products on the colonic microbiome were investigated by monitoring bacterial growth and metabolites. Results demonstrated that both the prodrug and formulation approaches resulted in a similar percentage of 5-ASA recovery under healthy conditions. On the contrary, during experiments simulating the GI physiology and microbiome of IBD patients (the target population) the formulation strategy resulted in a higher proportion of 5-ASA delivery to the colonic region as compared to the prodrug approach (P < 0.0001). Interestingly, the two products had distinct effects on the synthesis of key bacterial metabolites, such as lactate and short chain fatty acids, which varied according to disease state and ileal pH variability. Further, both 5-ASA and sulfasalazine significantly reduced the growth of the faecal microbiota sourced from six healthy humans. The findings support that the approach selected for colonic drug delivery could significantly influence the effectiveness of UC treatment, and highlight that drugs licensed for UC may differentially impact the growth and functioning of the colonic microbiota.

[Statins under fire: justified or not?]. / Les statines sous les feux de la critique: a tort ou a raison?

Statins inhibit the synthesis of cholesterol in the liver resulting in a decrease of LDL cholesterol and triglycerides, and a limited increase in HDL cholesterol. Statins also have pleiotropic effects, such as stabilisation of atherosclerotic plaques. The 4S-study was the first trial that demonstrated a significant benefit with statins in secondary prevention. The WOSCOPS-study was the first to prove the efficacy of statins in primary prevention. diseases approximately 10 years later than men. Therefore, it looks as if women are protected against cardiovascular diseases. Hence, they were underrepresented in large clinical trials. If there is no limited life expectancy, elderly--even older than 85 years--do not have to be treated differently for the secondary prevention than younger people. For primary prevention, the situation of the patient has to be evaluated, paying attention to additional risk factors. Type 2 diabetic patients that already have had a cardiovascular incident are considered to be at high risk and are eligible for an intensive therapy. Primary prevention in diabetic patients is often compared with secondary prevention in non-diabetic patients. The use of statins in children is controversial due to possible interference with the development of the child. New guidelines decrease the age for starting a therapy from 10 years old to 8 years old. For all patients a good safety profile is very important, given the long duration of therapy. Statins are used increasingly in high dose and accordingly the risk of adverse effects increases. Muscle toxicity is the most frequent side effect. The risk is strongly intensified by drug interactions through CYP3A4 (for simvastatin and atorvastatin), high doses, and combination therapy with fibrates. The use of statins during pregnancy is contra-indicated. Pharmacists are well placed to give advice about the risks of the use, or non-use, of statins. A high cholesterol level and the accompanied risk of cardiovascular disease, is something that one cannot really sense. The well-established effects of statins have to be explained to patients, together with a healthy life style. It is important to mention that the effects of statins in high--risk patients are largely proven. For primary prevention the risk factors have to be evaluated individually. Compliance is often low and pharmacists can play a major role in the pharmaceutical care of cardiovascular patients.