Drivers of absolute systemic bioavailability after oral pulmonary inhalation in humans.

There are few studies in humans dealing with the relationship between physico-chemical properties of drugs and their systemic bioavailability after administration via oral inhalation route (Fpulm). Getting further insight in the determinants of Fpulm after oral pulmonary inhalation could be of value for drugs considered for a systemic delivery as a result of poor oral bioavailability, as well as for drugs considered for a local delivery to anticipate their undesirable systemic effects. To better delineate the parameters influencing the systemic delivery after oral pulmonary inhalation in humans, we studied the influence of physico-chemical and permeability properties obtained in silico on the rate and extent of Fpulm in a series of 77 compounds with or without marketing approval for pulmonary delivery, and intended either for local or for systemic delivery.

Association between Functional Inhibitors of Acid Sphingomyelinase (FIASMAs) and Reduced Risk of Death in COVID-19 Patients: A Retrospective Cohort Study.

Given the current scarcity of curative treatment of COVID-19, the search for an effective treatment modality among all available medications has become a priority. This study aimed at investigating the role of functional inhibitors of acid sphingomyelinase (FIASMAs) on in-hospital COVID-19 mortality. In this retrospective cohort study, we included adult in-patients with laboratory-confirmed COVID-19 between 1 March 2020 and 31 August 2020 with definite outcomes (discharged hospital or deceased) from Erasme Hospital (Brussels, Belgium).

Drug-Drug Interactions in Elderly Patients with Potentially Inappropriate Medications in Primary Care, Nursing Home and Hospital Settings: A Systematic Review and a Preliminary Study.

Drug-drug interactions (DDI) occurring with potentially inappropriate medications (PIM) are additional risk factors that may increase the inappropriate character of PIM. The aim of this study was (1) to describe the prevalence and severity of DDI in patients with PIM and (2) to evaluate the DDI specifically regarding PIM. This systematic review is based on a search carried out on PubMed and Web-of-Science from inception to June 30, 2020.

Repurposing functional inhibitors of acid sphingomyelinase (fiasmas): an opportunity against SARS-CoV-2 infection?

What Is Known And Objective: Infection by SARS-CoV-2, the virus responsible of COVID-19, is associated with limited treatment options. The purpose of this study was to evaluate the rationale for repurposing functional inhibitors of acid sphingomyelinase (FIASMAs), several of which are approved medicines, for the treatment of SAR-CoV-2 infections.

Comment: We propose and discuss the FIASMAs' lysosomotropism as a possible explanation for their observed in vitro activities against viruses, and more specifically against infections caused by coronaviruses such as SARS-CoV-2.

Risk of acute kidney injury by initiation of non-steroidal anti-inflammatory drugs in hospitalised patients treated with diuretics and renin-angiotensin-aldosterone system inhibitors.

Objectives: Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) with diuretics and renin-angiotensin-aldosterone system inhibitors (RAASI) has been associated with an increased risk of developing acute kidney injury (AKI) in the ambulatory setting. There is currently no information on AKI prevalence in hospitalised patients where initiation of NSAID prescription is quite frequent. The aim of our study was to assess the prevalence of AKI in patients treated with diuretics and/or RAASI in the hospital setting when NSAIDs are initiated.

Maternal and Fetal Blood Pharmacokinetics and Organ Distribution of Atrazine, Propazine, Simazine, and Their Metabolites in Pregnant Rats After Chronic Oral Administration.

Environmental contamination by chlorotriazines has been evidenced in mother-child cohort suggesting more detailed risk assessment of these compounds in drinking water. Exposure of rodents to atrazine (ATZ) has been associated with alterations of endocrine and reproductive functions by disrupting neuroendocrine control at hypothalamus level. Perinatal exposure to low doses of ATZ has been associated with reproductive dysfunction, and to behavioral abnormalities in adult exposed during embryogenesis.

A case report of photodermatoses induced by the antifungal drug terbinafine.

Terbinafine is an antifungaldrug(inhibitor of ergosterol synthesis) known to induce skin reactions. A 58-year-old female was treated with terbinafine for onychomycosis. On the fifth day of treatment a skin rash emerged on her sun-exposed areas.

Prescriptome analytics: an opportunity for clinical pharmacy.

Clinical pharmacists have unique opportunities to be more involved in prescriptome analytics to expand research horizon in clinical pharmacy as an academic discipline. The development of predictive analytics with machine learning algorithms could have the potential to redesign the way we care for patients in our institutions for a more personalized medication therapy.

Potential drug-drug interactions and nephrotoxicity in hematopoietic stem cell transplant adult recipients during bone marrow transplantation unit stay.

Purpose: Studies have documented potential drug-drug interactions (pDDIs) occurring in cancer patients mainly with solid malignancies, either in the ambulatory or hospital settings. While hematopoietic stem cell transplant (HSCT) patients during their bone marrow transplantation unit (BMTU) stay have rather complex medical regimens combining chemotherapy, anti-infectious agents, immunosuppressive agents, and supportive-care drugs, studies on potential DDIs are lacking. Our objective was to evaluate the prevalence and the density of pharmacokinetic and pharmacodynamic potential DDIs, and the evolution of the renal function in hematopoietic stem cell transplant (HSCT) adult recipients during their BMTU stay.

Prevalence and nature of statin drug-drug interactions in a university hospital by electronic health record mining.

Aim: Our aim was to describe prevalence, nature, and level of severity of potential statin drug-drug interactions in a university hospital.

Methods: In a cross-sectional study, statin drug-drug interactions were screened from medical record of 10,506 in-patients treated stored in the clinical data warehouse "eHOP." We screened drug-drug interactions using Theriaque and Micromedex drug databases.

Clinical pharmacokinetics of oral drugs in the treatment of multiple myeloma.

Treatment of myeloma is a long-term treatment mainly based on all-oral combinations of drugs. Because oral drugs have a more complex pharmacokinetics compared with IV treatments, an appropriate knowledge of the factors that may alter their systemic exposure is of particular clinical relevance. Both drug-drug interactions, food-effect, and dose-adaptation in renal and hepatic impairment may influence the systemic drug levels with a potential impact on drug efficacy or safety.

Pharmacokinetic drug-drug interactions of tyrosine kinase inhibitors: A focus on cytochrome P450, transporters, and acid suppression therapy.

The extensive use of tyrosine kinase inhibitors (TKI's) in hematology and oncology has shown that these drugs have a significant potential for drug-drug interactions. Since these drugs have a rather low therapeutic window, some drug interactions are of particular clinical relevance either on drug toxicity or on patient's response. Significant interactions occur with concomitant use of acid-suppressive therapy leading to a decreased oral bioavailability.

Population Pharmacokinetics of Amitriptyline After Intrathecal, Epidural, and Intravenous Administration in Sheep.

Background: Amitriptyline (AMI) is a lipophilic, tricyclic antidepressant with analgesic properties that could potentially be used for epidural (EPI) analgesia. However, no pharmacokinetic data are available for AMI in spinal spaces. The objective of this study was to evaluate the spinal disposition and intrathecal (IT) bioavailability of AMI after IT and EPI administration.