Study of compatibility of components of a new combined drug for treatment of alcoholic intoxication and its hepatoprotective effect on a model of alcoholic liver injury

The aim of the work is the development of a combined drug for use in alcohol intoxication based on the physicochemical properties and chemical compatibility of active pharmaceutical ingredients and excipients, and the study of the hepatoprotective effect in alcoholic hepatitis in rats. Materials and methods. During the studies, physical and physicochemical methods were used, a Specord 200 spectrophotometer (Germany), analytical scales Sartorius (SARTORIUS, Germany), class A volumetric glassware and reagents that meet the requirements of the State Pharmacopoeia of Ukraine (SPhU). Alcoholic hepatitis in rats was reproduced by intragastric administration of an aqueous 40% ethanol solution at a dose of 7 ml/kg for 1 week. Results. A new combined agent is proposed for use in alcohol intoxication in the form of an effervescent powder for the preparation of an oral solution, which contains glycine, L-glutamic acid, acetylsalicylic acid, ascorbic acid, fructose / sorbitol and sodium bicarbonate and citric acid to accelerate the dissolution of medicinal substances. To study the compatibility of the components, experimental studies of hygroscopicity, chemical interaction / chemical stability and an assessment of the redox potential of the proposed active pharmaceutical ingredients were carried out. To study the stability of the API, studies were carried out on sugaramine condensation due to the choice of amino acids and ascorbic acid in the composition of drugs. Based on the research results, it was decided to divide the API into 2 packages, separating sodium bicarbonate and glycine, which can interact with ascorbic acid / acetylsalicylic acid and ascorbic acid, respectively. In an in vivo experiment, it was found that the use of the new drug is accompanied by the normalization of the antioxidant-prooxidant status of the liver due to a likely decrease in the TBA-AP level and an increase in the RG index in the liver homogenate relative to the control group. Conclusions. Evaluation of the physicochemical properties of API allowed us to propose a new combined drug (TS-PP) for use in alcohol intoxication in the form of an effervescent powder for the preparation of oral solution. In alcoholic hepatitis in rats, it was found that the use of the studied drug largely prevents the formation of the effects of the toxic effects of ethanol on the rat organism, which is manifested by inhibition of destruction of hepatocyte membranes, a decrease in the level of LPO products, restoration of the RG index and improvement of the protein synthesizing function of the liver due to the complex effect of amino acids and ascorbic acid contained in the product

Prognostic Factors of In-Hospital Mortality in Adult Patients With Aluminum Phosphide (ALP) Poisoning in Southern Iran (2014-2018)

Background: The suicide with aluminum phosphide, known as rice tablet, has increased significantly. This study aimed to investigate the epidemiology of Aluminum Phosphide (ALP) poisoning and determine the in-hospital mortality prognostic factors in adult people referring to ALP poisoning to one of the main poisoning centers in southern Iran. Methods: This retrospective cross-sectional study (March 21, 2014, to March 21, 2018) was conducted on all adult patients (>16 years) with ALP poisoning who were referred to Ali-Asghar Hospital (affiliated with Shiraz University of Medical Sciences). All data were extracted from the patients’ medical files. The patients were categorized into two groups of survived and non-survived. Univariate and multivariate logistic regression analyses were conducted to determine prognostic factors for in-hospital mortality, and Odds Ratios (ORs) were reported. Results: Totally, 97 patients were enrolled in this study. The patients’ Mean±SD age was 29.3±12.2 years. Both study groups (survived and non-survived) were matched in most demographic and poisoning characteristics. Nausea (62.9%) and vomiting (49.5%) were the most symptoms at the time of admission. Castor oil (66%), N-acetyl cysteine (56.7%), and magnesium sulfate (52.6%) were the most frequent treatment in these patients. The multivariate analysis showed that age (OR=1.12, 95%CI: 1.03-1.22), body temperature (OR=0.02, 95%CI: 0.01-0.48), resistant acidosis (OR=77.10, 95%CI: 5.05-1176.86), and taking sodium bicarbonate (OR=12.35, 95%CI: 1.25-122.10) were the prognostic factors of in-hospital mortality. Conclusion: The in-hospital mortality rate in patients with ALP poisoning was 29.9%. Age, illiteracy, body temperature, resistant acidosis, and taking sodium bicarbonate were the prognostic factors of in-hospital mortality in these patients.

Retrospective evaluation of sodium acetate use for urine alkalinization in patients receiving high dose methotrexate

Purpose Methotrexate is an antifolate agent used in treatment of several malignancies. Many toxicities accompany methotrexate that are minimized with urine alkalinization. Parenteral sodium bicarbonate is the historical standard alkalinizing agent, but use has been limited by intermittent shortages. However, intravenous sodium acetate may be considered as a chemically equivalent alternative. The primary objective of this study is to determine the efficacy of sodium acetate versus sodium bicarbonate for urine alkalinization for high-dose methotrexate (HDMTX). Methods This is a retrospective cohort study including adults admitted to Barnes-Jewish Hospital to receive HDMTX for lymphoma, breast cancer with leptomeningial spread, or osteosarcoma. Patients must have received intravenous sodium acetate or sodium bicarbonate alkalinization. Results Of 192 HDMTX encounters, 154 (sodium bicarbonate, n = 86; sodium acetate, n = 68) were evaluated for efficacy and safety. Safety outcomes were not significantly different between groups except for higher peak methotrexate level in the bicarbonate group (2.9 mcmol/L vs. 1.7 mcmol/L, p = 0.023), and increased incidence of grade 3–4 ALT in the sodium bicarbonate group (23.5% vs. 9%, p = 0.02). Time from alkalinizer initiation to pH ≥7 was significantly shorter with sodium bicarbonate (4 vs. 5.15 h, p = 0.021). Nonetheless, outcomes such as length of stay (4.4 vs. 4 days respectively, p = 0.037) and time to methotrexate clearance (3.6 vs. 3.2 days respectively, p = 0.023) reveal that inpatient time was shorter with sodium acetate overall. Conclusion This retrospective analysis suggests that sodium acetate has similar efficacy and safety to sodium bicarbonate for alkalinization and may be considered as an alternative in future shortage situations.