Machine Learning-Based Prediction of Drug-Drug Interactions for Histamine Antagonist Using Hybrid Chemical Features

The requesting of detailed information on new drugs including drug-drug interactions or targets is often unavailable and resource-intensive in assessing adverse drug events. To shorten the common evaluation process of drug-drug interactions, we present a machine learning framework-HAINI to predict DDI types for histamine antagonist drugs using simplified molecular-input line-entry systems (SMILES) combined with interaction features based on CYP450 group as inputs. The data used in our research consisted of approved drugs of histamine antagonists that are connected to 26,344 DDI pairs from the DrugBank database. Various classification algorithms such as Naive Bayes, Decision Tree, Random Forest, Logistic Regression, and XGBoost were used with 5-fold cross-validation to approach a large-scale DDIs prediction among histamine antagonist drugs. The prediction performance shows that our model outperformed previously published works on DDI prediction with the best precision of 0.788, a recall of 0.921, and an F1-score of 0.838 among 19 given DDIs types. An important finding of the study is that our prediction is based solely on the SMILES and CYP450 and thus can be applied at the early stage of drug development.

Maternal Transfer of Cetirizine Into Human Milk

Introduction Cetirizine hydrochloride is a second-generation H1 histamine antagonist with Food and Drug Administration approval for treatment of allergic rhinitis and urticaria. Currently, the Food and Drug Administration does not recommend use of cetirizine during breastfeeding, as there are insufficient studies on both the transference of cetirizine into human milk and the effects of cetirizine in infants. Main issue To determine the concentration of cetirizine in human milk, samples were analyzed using high performance liquid chromatography mass spectrometry. Management Based on calculations, relative infant dose was found to be 1.77% at 24 hr. In addition, there were no reported adverse effects seen in the infants. Conclusion We suggest that transfer of cetirizine into human milk is minimal and unlikely to pose a significant risk to the breastfeeding infant. This is the first report presenting the transfer of cetirizine in human milk.

The Involvement of the RhoA/ROCK Signaling Pathway in Hypersensitivity Reactions Induced by Paclitaxel Injection

A high incidence of hypersensitivity reactions (HSRs) largely limits the use of paclitaxel injection. Currently, these reactions are considered to be mediated by histamine release and complement activation. However, the evidence is insufficient and the molecular mechanism involved in paclitaxel injection-induced HSRs is still incompletely understood. In this study, a mice model mimicking vascular hyperpermeability was applied. The vascular leakage induced merely by excipients (polyoxyl 35 castor oil) was equivalent to the reactions evoked by paclitaxel injection under the same conditions. Treatment with paclitaxel injection could cause rapid histamine release. The vascular exudation was dramatically inhibited by pretreatment with a histamine antagonist. No significant change in paclitaxel injection-induced HSRs was observed in complement-deficient and complement-depleted mice. The RhoA/ROCK signaling pathway was activated by paclitaxel injection. Moreover, the ROCK inhibitor showed a protective effect on vascular leakage in the ears and on inflammation in the lungs. In conclusion, this study provided a suitable mice model for investigating the HSRs characterized by vascular hyperpermeability and confirmed the main sensitization of excipients in paclitaxel injection. Histamine release and RhoA/ROCK pathway activation, rather than complement activation, played an important role in paclitaxel injection-induced HSRs. Furthermore, the ROCK inhibitor may provide a potential preventive approach for paclitaxel injection side effects.

A Concise and Efficient Synthesis of an Impurity, N-Desmethyl Alcaftadine from Alcaftadine: An H1 Antagonist

Herein, a simple approach for the synthesis of N-desmethyl alcaftadine, an H1 histamine antagonist in solid state and its structure is presented. The reactions were performed under mild and metal free conditions at reflux temperature within a range of 65-70 ºC and the desired product N-desmethyl alcaftadine was obtained in high purity with good yield (96.42 %). It was detected by ultra-high-performance liquid chromatography (UHPLC).

The problem with treating sinusitis against the background of allergic rhinitis

Both allergic rhinitis (AR) and sinusitis are widespread diseases that significantly worsen the patient’s quality of life, lead to significant financial costs and are associated with a huge health burden. When treating any AS, it is necessary to follow three basic principles: address the cause of the disease; eradicate the pathogen; restore drainage of sinuses, aerate and restore CO. The efficacy and speed in the treatment of sinusitis, which arose against the background of allergic inflammation, are comparable to those in the use of oral GCS (Ib level, persuasion scale A). The H1-histamine receptor blocker and competitive histamine antagonist ebastine is one of the most effective and safe latest-generation antihistamine.

Photostability of Loratadine Inclusion Complexes with Natural Cyclodextrins

The purpose of this study was to evaluate the photostability of inclusion complexes of the histamine antagonist loratadine (LORA) withα-,β-, andγ-cyclodextrins (CDs). Accordingly, binary drug-CD complexes were prepared using the coevaporation method at 1 : 1, 1 : 2, and 1 : 3 stoichiometric ratios, which were characterized by thermal analysis. Subsequently, solutions of the complexes at 500 μg mL−1in HCl 0.1 M were subjected to irradiation in a photostability chamber for 12 hours, and the content of the remaining active ingredient was quantified by means of high-performance liquid chromatography. It is possible to observe the presence of two products originating from photodegradation (P1 and P2), which were identified in solutions of loratadine withα- andβ-CD. By means of statistical analysis, we conclude that the drug:α-CD and drug:γ-CD (1 : 1) complexes proved to be more efficient in the photostability assay, obtaining a nonsignificant level of degradation and full recovery of LORA.