Результаты поиска

Interaction of doxantrazole with calcium ions in solvents of intermediate polarity. Possible effect of ionization of the drug.

Spectral evidence is presented that 0.01-0.03 mM solutions of the antiasthmatic drug doxantrazole contain the neutral or ionized form, depending on the solvent and, at least in 1 case, on concentration. In 1,4-dioxane, where only the neutral form exists, and in water, where the drug is ionized, no reaction between doxantrazole and calcium ion can be demonstrated spectroscopically. However, in 2-propanol at 0.01 mM and in 7:3 (v/v) 1,4-dioxane-water the doxantrazole anion can be shown to react with calcium. In more concentrated 2-propanol solutions most of the drug is in the neutral form, and n

Liposome-cell interactions. A study of the interactions of liposomes containing entrapped anti-cancer drugs with the EMT6, S49 and AE1 (transport-deficient) cell lines.

A study has been made to determine if the cytotoxicity observed when cells in culture were exposed to liposome-entrapped cytotoxic drugs was liposome mediated or resulted from leakage of drug from the liposomes with subsequent uptake of free drugs by the cells. In preliminary experiments with the EMT6 cell line in monolayer culture, the cytotoxicity observed when the cells were exposed to a range of concentrations of liposome-entrapped methotrexate, actinomycin D and cytosine arabinoside for a variety of liposome compositions was somewhat less than that observed when the cells were exposed to

Safety, tolerability, and drug-drug interactions of NYX-783 and oxycodone in persons using opioids recreationally: Preliminary results from a randomized, double-blind, placebo-controlled phase 1 study.

BACKGROUND: Novel treatments are needed for opioid use disorder (OUD). NYX-783, an NMDA positive allosteric modulator, affects synaptic plasticity and learning, key processes in. Although prior preclinical and studies in healthy humans have established its safety and tolerability, studies are needed in the context of opioid use. METHODS: Nine men who used opioids recreationally and passed a safety session were enrolled in inpatient study. Participants received single doses of NYX-783 (50mg, 150mg) and placebo and in combination with two oxycodone doses (15mg, 30mg), across six inpatient drug-

Совместное управление триазолами с хемапаевыми и/или иммунозопрессивными агентами, известными умеренным взаимодействием между наркотиками и наркотиками у пациентов с гематологическими заболеваниями, госпитализировано в связи с инвазивным аспергиллозом.

ОБРАЩЕНИЕ: Триазолы широко используются для лечения и профилактики инвазивного аспергиллоза (ИА), но могут вызывать серьезное взаимодействие с наркотиками (ДПИ) с химиотерапией (ХТ) и иммунодепрессантами (ИС) посредством ингибирования CYP3A4. Частота получения трехазол-ХТ или одновременного лечения в случае гематологовых заболеваний (ГМ) вновь принятых в ПА пациентов в целом неизвестна. Мы изучили американские претензии IQVIA, в том числе в отношении взрослых ≥ 1 требование о пребывании в стационаре с диагностическим кодом для АИ с октября 1, 2015- ноябрь 30, 2022 и доказательства существовани

Совпадение в аннотации оригинала
BACKGROUND: Triazoles are widely used for treatment and prevention of invasive aspergillosis (IA) but can cause serious drug-drug interactions (DDIs) with chemotherapeutic (CT) and immunosuppressant (IS) agents via CYP3A4 inhibition. The frequency of triazole-CT or IS concurrent administration in hematologic malignancies (HM) patients newly admitted with IA …

Assessment of Drug-Drug Interactions between Taspoglutide, a Glucagon-Like Peptide-1 Agonist, and Drugs Commonly Used in Type 2 Diabetes Mellitus: Results of Five Phase I Trials.

BACKGROUND AND OBJECTIVE: Taspoglutide, a glucagon-like peptide-1 agonist, like native glucagon-like peptide-1, delays gastric emptying time and prolongs intestinal transit time, which may alter the pharmacokinetics of concomitantly administered oral drugs. The effect of taspoglutide on the pharmacokinetics of five oral drugs commonly used in patients with type 2 diabetes mellitus was assessed in healthy subjects. METHODS: Five clinical pharmacology studies evaluated the potential drug-drug interaction between multiple subcutaneous taspoglutide doses and a single dose of lisinopril, warfarin,

Clinical characteristics and drug-drug interactions in human epidermal growth factor receptor 2-positive breast cancer treated with trastuzumab deruxtecan: real-world data from the DE-REAL study.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) reshaped clinical practice in human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC). The impact of clinical characteristics and drug-drug interactions (DDIs) on outcomes in patients receiving T-DXd is still under investigation. METHODS: We retrospectively analyzed data of patients from the Italian DE-REAL study. Clinical features including age, body mass index (BMI), toxicity and DDIs were assessed and correlated with clinical outcomes. The Drug-PIN software was used to evaluate DDIs. RESULTS: Among 143 patients, a…

Differential Preincubation Effects of Nicardipine on OATP1B1- and OATP1B3-Mediated Transport in the Presence and Absence of Protein: Implications in Assessing OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions.

Impaired transport activity of hepatic OATP1B1 and OATP1B3 due to drug-drug interactions (DDIs) often leads to increased systemic exposure to substrate drugs (e.g., lipid-lowering statins). Since dyslipidemia and hypertension frequently coexist, statins are often concurrently used with antihypertensives, including calcium channel blockers (CCBs). OATP1B1/1B3-related DDIs in humans have been reported for several CCBs. To date, the OATP1B1/1B3-mediated DDI potential of CCB nicardipine has not been assessed. The current study was designed to assess the OATP1B1- and OATP1B3-mediated DDI potential …

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney.

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with Ki values (μM) of 0.030-0.28 and 2.4-5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with Km values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CLR) of trimet…

Paclitaxel in the treatment of human immunodeficiency virus 1-associated Kaposi's sarcoma--drug-drug interactions with protease inhibitors and a nonnucleoside reverse transcriptase inhibitor: a case report study.

PURPOSE: To describe the pharmacokinetics of paclitaxel and to investigate the interaction potential with protease inhibitors (indinavir, ritonavir, saquinavir) and the nonnucleoside reverse transcriptase inhibitor nevirapine, for which strong theoretical indications for clinically relevant drug interactions exist. METHODS: The 24-h plasma pharmacokinetics of paclitaxel (Taxol, given at 100 mg/m2 by 3-h intravenous infusion) and concomitantly infused antiretroviral drugs were determined in a human immunodeficiency virus 1 (HIV-1)-infected male patient with refractory Kaposi's sarcoma (KS) dur…

The in vivo metabolic pathway of Deg-AZM and in vitro investigations into the contribution of drug metabolizing enzymes and drug transporters in the drug interactions of Deg-AZM, a clinical-stage new transgelin agonist.

INTRODUCTION: Deglycosylated azithromycin (Deg-AZM), a new transgelin agonist with positive therapeutic effects on slow transit constipation, has been approved for clinical trials in 2024. This work investigated the drug metabolism and transport of Deg-AZM to provide research data for further development of Deg-AZM. METHODS: A combination of UPLC-QTOF-MS was used to obtain metabolite spectra of Deg-AZM in plasma, urine, feces and bile. Caco-2 cells was used to investigate the permeability of Deg-AZM and whether it is a potential substrate of the efflux transporter P-glycoprotein. Human liver

Simultaneous determination of three tyrosine kinase inhibitors and three triazoles in human plasma by LC-MS/MS: applications to therapeutic drug monitoring and drug-drug interaction studies.

Tyrosine kinase inhibitors (TKIs) and triazole antifungals are the first-line drugs for treating chronic myeloid leukemia (CML) and fungal infections, respectively, but both suffer from large exposure differences and narrow therapeutic windows. Moreover, these two types of drugs are commonly used together in CML patients with fungal infections. Multiple studies and guidelines have suggested the importance of therapeutic drug monitoring (TDM) of TKIs and triazoles. Currently, methods for the simultaneous determination of both types of drugs are limited. We developed a simple, rapid, and reliabl

The deformation energy gap in computational drug design: why interaction energy alone cannot rank drug candidates and a thermodynamic correction protocol.

DFT calculations are increasingly combined with molecular docking to rank drug candidates, yet most studies report the interaction energy (ΔEint), computed at the complex geometry, as a surrogate for binding affinity. This quantity omits the deformation energy (ΔEdef): the thermodynamic penalty of distorting both partners from their free-state geometries into their bound conformations. Because ΔEdef is always positive (typically 2-20 kcal mol-1) and molecule-dependent, its omission systematically overestimates binding strength and can reverse predicted rank-orderings. We present the energetic

Comparative thromboembolic risk and polypharmacy-related drug-drug interaction signals among antidiabetic medications: a large-scale FAERS pharmacovigilance study.

BACKGROUND: The relationship between antidiabetic drugs and thromboembolic events remains unclear. The FDA Adverse Event Reporting System (FAERS) data was used to systematically assess safety signals and polypharmacy-related drug-drug interactions of antidiabetic medications. METHODS: By analyzing FAERS reports from 2004 to 2025 that included antidiabetic drugs, the Reporting Odds Ratio (ROR), the Proportional Reporting Ratio (PRR), the Information Component (IC), and the Empirical Bayes Geometric Mean (EBGM) were used to assess disproportionality. Factors such as the main suspected drug, eve…

Преодоление разрыва в знаниях о беременности: реальный всемирный анализ потребления лекарств и риска взаимодействия наркотиков в болезни Крона и множественном склерозе.

Исключение беременных людей из клинических испытаний привело к значительному разрыву в уровне медицинских знаний для этого населения. Использование реальных данных (РВД) является важнейшим звеном в распространении и использовании лекарственных средств во время беременности. С помощью базы данных планов медицинского страхования " IQVIA Pharmetrics(R) Plus " мы провели оценку использования методов лечения заболеваний и сопутствующих лекарств у беременных. Мы сосредоточились на two примеры: болезнь Крона (CD) и множественный склероз (MS)-анализирующие пациенты с историей использования D

Совпадение в полном тексте источника
… Concomitant Medication Analysis To assess potential drug–drug interaction (DDI) risks, the top 100 prescribed medications in each disease cohort were identified from the IQVIA PharMetrics(R) Plus database. … The top 100 conmeds prescribed during pregnancy for both disease cohorts identified the potential for drug–drug interactions (DDIs) mediated by CYP450s and drug transporters. …

Использование данных о реальных требованиях для оценки распространенности конкомитативных лекарств для информирования о риске взаимодействия между наркотиками и наркотиками среди целевых групп пациентов.

Одной из общих проблем в области развития клинических наркотиков является взаимодействие между наркотиками и наркотиками (ДДИ), которое может привести к изменению воздействия наркотиков и последующему изменению безопасности и эффективности следственного препарата или сопутствующих ему лекарственных препаратов (кондекций) среди целевой группы пациентов. Таким образом, трубопровод для разработки лекарств включает оценку рисков, связанных с диагностикой наркотиков, на основе исследований in vitro, моделирования силико и клинических испытаний. Данные о реальном мире (ДСР), в частности базы данных

Совпадение в аннотации оригинала
A common issue in clinical drug development involves drug-drug interactions (DDI) that may lead to altered drug exposure and subsequent altered safety and efficacy of an investigational drug or concomitant medications (conmeds) in the target patient population. The drug development pipeline therefore involves DDI risk assessment of the investigational drug b…

Pharmacokinetics and Safety of Atogepant Co-administered with Quinidine Gluconate in Healthy Participants: A Phase 1, Open-Label, Drug-Drug Interaction Study.

Atogepant, an oral calcitonin gene-related peptide receptor antagonist, is approved for the preventive treatment of migraine. Atogepant is a substrate of P-glycoprotein (P-gp), breast cancer resistance protein, organic anion transporting polypeptide transporters, and cytochrome P450 (CYP)3A4 and 2D6. Quinidine is a strong P-gp and CYP2D6 inhibitor. A phase 1 open-label study evaluated the effect of P-gp and CYP2D6 inhibition by quinidine on the pharmacokinetics of atogepant, and the safety and tolerability of atogepant and quinidine gluconate (QG) when co-administered and when given alone in 3

Retrospective Analysis of Potential Adverse Drug Interactions in the Drugs Prescribed to the Elderly at a Tertiary Health Care Center in Raipur, Chhattisgarh, Central India.

Background The elderly population differs from adults in having various physiological changes and multiple diseases, which demand the use of multiple medications. The practice of polypharmacy in the elderly leads to numerous harmful effects like adverse drug reactions, adverse drug-drug interactions (DDIs), poor compliance, etc. Methodology This study collected 295 case files of elderly patients retrospectively in the Departments of General Medicine, Cardiology and Nephrology after obtaining Institute Ethics Committee approval to look for the potential adverse DDIs with their severity accordin…