Drug-drug Interaction

The study treatment BAY3389934 is under development for people with blood clotting problems that occur due to sepsis. Sepsis is a serious condition that happens when the body's reaction to an infection causes organ damage. It can eventually lead to tiny blood clots formation throughout the body. BAY3389934 aims to work by blocking two important blood clotting proteins, called Factor IIa (thrombin) and Factor Xa, both of which help in blood clotting. By blocking them, BAY3389934 may slow down or stop excessive clotting. Aspirin is a drug that prevents platelets from clumping together. People with sepsis are often given aspirin for underlying heart-related problems. Since aspirin and BAY3389934 both affect how the blood clots, each in a different way, it is important to check whether using them together is safe and whether they change each other's effects on blood clotting. The main purpose of this study is to find out how safe BAY3389934 is when given together with aspirin and to see how the two affect blood clotting in healthy participants. To do this, the researchers will assess the number and severity of medical problems in healthy adult participants after receiving BAY3389934 alone and in combination with aspirin and compare them with the medical problems when participants received either drug alone. These medical problems are also known as "adverse events". Doctors keep track of all medical problems that happen in studies, even if they do not think they are related to study treatments. All participants will receive a single dose of aspirin tablet prior to the study. Researchers will check their response to decide whether they can participate in the study. Eligible participants will then receive the following three treatments, each at different time and in a different order assigned randomly. Treatment A: * no treatment the day prior to receiving study treatment. * BAY3389934 as an infusion into a vein on Day 1. Treatment B: * a single high-dose aspirin tablet on the day prior to receiving study treatment. * a single-low dose aspirin tablet on Day 1. Treatment C: * a single high-dose aspirin tablet on the day prior to receiving study treatment. * a single low-dose aspirin tablet followed by BAY3389934 4 hours continuous infusion into a vein on Day 1. There will be a gap of 3 days after Treatment A, and 14 days after Treatments B and C, when participants will not be given any treatment. Each participant will be in the study for around 2 months with up to 6 visits to the study clinic. They will visit the study clinic: * twice, before the treatment starts * once, during each of the three treatment periods * once, at the end of the treatment During the study, the doctors and their study team will * check participants' health by performing tests such as blood and urine tests, measuring blood pressure, heart rate and checking heart health using an electrocardiogram (ECG). * ask the participants questions about how they are feeling and any adverse events they are having. In this study, the participants will not benefit from taking of BAY3389934. However, the study will provide information on how BAY3389934 may be helpful in people with blood clotting problems caused due to sepsis.

The main goal of this clinical study is to test how CYP2B6 genetic variations and efavirenz (cornerstone in HIV-1 therapy) dictate the disposition (PK) of CYP2B6 substrate (methadone) and PK and effect (PD) of CYP1A2 substrate (tizanidine). Specifically, the investigators will test whether efavirenz produces CYP2B6 genotype dependent unanticipated DDIs with CYP2B6 (methadone) and CYP1A2 (tizanidine), leading to lack of efficacy or increased toxicity. Healthy volunteers genotyped for CYP2B6\*6 and \*18 alleles will be grouped in to three genotype predicted phenotype groups: 20 normal metabolizer (NM) (CYP2B6\*1/\*1); 20 intermediate metabolizer (IM) (\*1/\*6, or \*1/\*18); and 20 poor metabolizer (PM) (\*6/\*6, \*6/\*18 or \*18/\*18). Each phenotype group will receive methadone and tizanidine (separated by a washout period) on two occasions: at baseline (control) and after treatment with efavirenz (600 mg/day for 17 days).

This study is being done to understand how long-acting injectable cabotegravir (CAB-LA) used for HIV pre-exposure prophylaxis (PrEP) and hormonal contraceptive methods affect each other when used at the same time. Women who are already using CAB-LA or not using PrEP will choose to join one of several groups based on whether they use injectable contraceptive (IM DMPA), an etonogestrel implant, or no hormonal contraceptive. Participants will have study visits every 4 to 12 weeks for up to 12 or 24 weeks after starting a contraceptive method to collect blood samples and measure levels of CAB-LA and hormone concentrations. The study will compare these levels to see if taking CAB-LA changes hormone concentrations or if using hormonal contraception changes CAB-LA drug levels. Safety, side effects, satisfaction, and continuation of CAB-LA PrEP and contraceptive methods will also be evaluated.

The study investigators are conducting foundational pharmacokinetic (PK) and qualitative studies, among 15-24 years old (inclusive) adolescent girls and young women living with HIV (AGYWLHIV) already on oral antiretroviral therapy (ART) and virally suppressed, leading up to a hybrid type I effectiveness-implementation trial randomizing individual AGYWLHIV to receive long-acting (LA) injectable cabotegravir/rilpivirine vs. standard of care within one of Kenya's largest HIV treatment programs. The PK and qualitative studies will investigate potential issues arising from co-delivery and guide delivery of the effectiveness-implementation trial. The PK and qualitative studies will largely be conducted with a sentinel cohort of AGYWLHIV. Learning from this early LA ART use, the investigators will refine the procedures in the LA ART hybrid trial.

Ketamine is a dissociative anesthetic developed approximately 60 years ago. Both ketamine and its isomer, esketamine, have been used for over 20 years in the treatment of treatment-resistant depression. Other treatment options for this type of depression include combinations of antidepressants, other medications used in depression treatment (such as lithium), psychotherapy, electroconvulsive therapy, and repetitive transcranial magnetic stimulation. The advantage of ketamine and its stereoisomer, esketamine, over other treatment options is their rapidly emerging antidepressant effect, which becomes apparent within the first few days of treatment. Ketamine is primarily metabolized by the cytochrome P450 (CYP) 3A4 enzyme, but also by the CYP2B6 and CYP2C9 enzymes. However, information on the significance of these different enzymes in ketamine metabolism is incomplete. Due to extensive first-pass metabolism, the bioavailability of orally administered ketamine varies significantly and is, on average, only 8-24%. This makes ketamine unsuitable for oral administration. In the treatment of depression, ketamine is administered as a slow intravenous infusion. The concurrent use of medications that inhibit ketamine metabolism can significantly increase the bioavailability of orally administered ketamine. Cobicistat is a potent inhibitor of the CYP3A4 enzyme, which can significantly increase ketamine bioavailability and reduce interindividual variability by inhibiting ketamine's CYP3A4-mediated metabolism. This might enable the oral use of ketamine. Cannabidiol is a cannabinoid that does not have addictive effects, but may have antidepressant and anxiolytic effects. Cannabidiol might reduce the dissociative side effects associated with ketamine treatment. Clinically, cannabidiol appears to moderately inhibit CYP enzymes in the order of potency: CYP2C19 \> CYP2C9 \> CYP3A \> CYP1A2, and based on in vitro data, it also somewhat inhibits the CYP2B6 enzyme, which is involved in ketamine metabolism. However, its effect on ketamine concentrations cannot be assessed based on current knowledge. The purpose of this study is to investigate the potential effects of cannabidiol, cobicistat, and their concurrent administration on the pharmacokinetics of orally administered ketamine. A secondary objective is to study the effect of cannabidiol on ketamine-induced side effects. Study Methodology: This is a four-phase, randomized, open-label, crossover study involving 12 healthy volunteers. On study days, participants will receive a 56 mg oral dose of ketamine in the research facility, alternately with water, cannabidiol, cobicistat, or both cannabidiol and cobicistat. There will be at least a two-week washout period between study days. The pharmacokinetics of ketamine and other study drugs will be investigated by taking blood samples according to a separate schedule for 11 hours after administration on the study day and the following morning. Pharmacokinetic parameters will be calculated from plasma concentrations of ketamine, cobicistat, cannabidiol, and their metabolites. The primary outcome measure is the total area under the curve (AUC0-∞) of ketamine. Additionally, the effects of the drugs on blood pressure, heart rate, and subjective adverse feeling of the study participants will be examined.

The healthcare systems are under increasing pressure due to a rise in emergency consultations, staff shortages, an ageing population and rising costs. Emergency departments are seeing more vulnerable patients, including elderly people, who are often on multiple medications and at risk of medication errors. To improve safety, the integration of pharmacists specialising in emergency medicine has proven beneficial: their presence in the team improves the detection of medication-related problems, speeds up and optimises treatment, reduces rehospitalisations and lowers healthcare costs. However, in most countries, these pharmacists are still rarely found in emergency departments, mainly due to a lack of resources and clinical prioritisation criteria tailored for them and adapted to this environment. Frailty screening tools and scores, such as ISAR, can be used to identify the elderly patients most at risk, predict adverse events such as fall or mortality, and thus adapt their care in the emergency department. Indeed, elderly frail patients often take many medications and consequently are at risk of medication errors, adverse events, inappropriate prescriptions or serious drug interactions. These patients may therefore require a specialised review on their medication by clinical pharmacists when they are admitted to the emergency department, but their high number make it impossible to care for all of them. We aim thus to evaluate the association between frailty (according to the ISAR score) and medication-related problems among elderly patients admitted to the emergency department. Researchers will examine whether this score can predict the presence of inappropriate prescribing and high-risk drug interactions. If so, pharmacists would then have a quick and easy tool to prioritise patients who would benefit most from a specialised review of their medications when they visit the emergency department. There will not be any intervention and this study will not influence patients care. Once patients agree to participate, researchers will prospectively collect medical data from elderly patients admitted to the emergency department and analyse their medical history, home medication, reason for admission, frailty score using ISAR, and perform a pharmaceutical analysis based on these data.

The goal of this observational study is to enhance the ability to forecast kidney failure in liver transplant patients in the ICU under multidrug treatment by developing a computer platform that integrates mathematical models of drug interactions, proteomics, and clinical data. The main outcomes it aims to develop are: 1. Design the multidrug web computing platform with available information on drug pair interactions (DDIs). 2. Integrate the proteomic and clinical data of liver transplant patients into the IT platform. 3. Implement the multidrug web platform to predict the clinical evolution of liver transplant patients.

This study aims to assess the prevalence and the outcome of prescribing drugs known to have major drug-drug interactions with anti-tuberculous drugs among Kasr Alainy tuberculous patients.