The effect of intravenous isosorbide dinitrate in acute decompensated heart failure in hospital.

Background According to new recommendations for the management of acute decompensated heart failure (ADHF) in 2015, intravenous vasodilator therapy might be given as an early therapy when systolic blood pressure is normal to high (≥110 mmHg). Only 29% of patients with ADHF are treated with vasodilators without medical contraindication. Objective To evaluate the effect of the systematic use of ISDN on ADHF without contraindication especially on rehospitalization rate. Settings The 600-bed hospital (Centre Hospitalier de l'Ouest Vosgien, Neufchâteau, France). Methods This is a retrospective study with data analysed from medical records. Patients with ADHF episodes and hospitalization in the cardiology department or intensive care unit (ICU) between November 2013 and December 2015 were included resulting in 199 hospitalizations in the analysis (37 were treated by ISDN, and 162 were not). Main outcome measure Effects of ISDN on 180-day hospital readmission for ADHF or acute myocardial infarction (AMI), in-hospital mortality, length of stay, number of ICU admissions, and ICU length of stay. Results Patients who received ISDN required more ICU admissions than the other patients (54.1 vs 33.3%, p = 0.02). Nevertheless 180-day hospital readmission was lower for patients who were receiving ISDN (8.1 vs 22.8%, p = 0.04). ISDN did not influence other clinical outcomes tested. Conclusion ISDN may minimize or prevent the consequences of altered haemodynamics. Lower rehospitalization rate with ISDN was seen in this study.

Effect of intravenous hydration in patients receiving bisphosphonate therapy.

BACKGROUND: Patients with advanced cancers are at high risk for bone metastases, which accelerate bone resorption and skeletal complications. Therefore, bisphosphonates, which are strong inhibitors of bone resorption, are widely used to prevent pathological fractures, pain and tumour-induced hypercalcaemia. Intravenous infusion of bisphosphonate is associated with dose- and infusion rate-dependent adverse renal effects. OBJECTIVE: The present study investigated the effect of hydration on bisphosphonate efficacy and safety. SETTINGS: The 600-bed CHOV Hospital (Neufchâteau, France) and the Université de Lorraine (Nancy, France). METHODS: Patients who received pamidronate or zoledronic acid treatments were identified: 50 patients [16 of whom were hydrated and 34 of whom were non-hydrated]. Data on serum calcium levels, creatinine clearance and clinical tolerance were collected. Main outcome measure The impact of hydration on these parameters was analysed between day 1 and day 7. RESULTS: Bisphosphonate normalized calcaemia and hydration did not induce further reduction of calcium levels. Patient kidneys were significantly preserved by hydration in both groups (median clearance: +6.2%), whereas dehydrated patients had lower creatinine clearance (median clearance: -1.1%). Hydration did not influence other clinical or biological parameters tested. CONCLUSION: Hydration plays an important role in the treatment of hypercalcaemia by pamidronate and zoledronic acid: it enhances kidney protection (i.e., creatinine clearance).

Microemulsions for oral administration and their therapeutic applications.

INTRODUCTION: The microemulsion concept was introduced in 1943 by Hoar and Schulman. Self-microemulsifying drug delivery systems (S(M)EDDS) are much more recent and can be described as isotropic solutions of oils and surfactants that form oil-in-water O/W microemulsions when they are poured into an aqueous medium. When they are presented as soft capsules for oral delivery, S(M)EDDS have the ability to considerably improve the intestinal absorption of agents that are incorporated into the S(M)EDDS. Forty percent of newly discovered drug candidates have little or no water solubility and therefore have low and/or variable bioavailability profiles. Many of these drugs are good candidates for formulation into S(M)EDDS. AREAS COVERED: This paper describes the preparation and assessment of these formulations and their current applications. The characterisation of this type of formulation has improved, and in vitro models (Caco-2 cell cultures, Ussing chambers, the everted sac technique, etc.) can be used for screening different formulations. It describes also marketed formulations (i.e., cyclosporin and saquinavir S(M)EDDS) and some other formulations. EXPERT OPINION: Actual applications of S(M)EDDS remain rare. The first drug marketed as a S(M)EDDS was cyclosporin, and it had significantly improved bioavailability compared with the conventional solution. In the last decade, several S(M)EDDS loaded with antiviral drugs (e.g., ritonavir, saquinavir) were tested for treatment of HIV infection, but the relative improvement in clinical benefit was not significant. The S(M)EDDS formulation of Norvir® (soft capsules) has been withdrawn in some countries.

Development of microemulsion of mitotane for improvement of oral bioavailability.

BACKGROUND: Mitotane (o,p'-DDD) is considered to be the drug of choice in the treatment of nonresectable and metastasized adrenocortical carcinoma. However, mitotane has poor solubility in the gastrointestinal tract and very low bioavailability. Consequently, to achieve therapeutic plasma level, high cumulative doses (4-6 g/day) of mitotane were usually used during 3-5 months. To shorten this equilibration time and reduce gastrointestinal side effects, a self-microemulsifying drug delivery system (SMEDDS) of mitotane has been developed. METHOD: First time, the solubility of mitotane was determined in various oils and surfactants; then, the influence of oils, surfactants, and cosurfactants on the formation of SMEDDS was investigated by constructing ternary phase diagrams. SMEDDS was characterized by morphological observations and droplet size measurements. Intestinal drug permeation of SMEDDS of mitotane (3 mM) was assessed in an Ussing-type apparatus and the bioavailability was determined in a rabbit model. RESULTS: The optimum formulation consisted of a mixture of Capryol, Tween, and Cremophor EL (33:33:33). The formulation was found to pass through the intestinal barrier much faster than a solution of mitotane (14.85 +/- 0.8 versus 3.03 +/- 0.2 micromol/cm(2)). Moreover, after oral administration in rabbits, the relative bioavailability was 3.4, compared with that of the conventional form (Lysodren). CONCLUSION: This SMEDDS can now be considered as a very good candidate to optimize the administration of mitotane.