Safety and Efficacy of ApTOLL in Patients With Ischemic Stroke Undergoing Endovascular Treatment: A Phase 1/2 Randomized Clinical Trial

Pubmed-Investigación

JAMA Neurol. 2023 Jun 20:e231660. doi: 10.1001/jamaneurol.2023.1660. Online ahead of print. ABSTRACT IMPORTANCE: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. OBJECTIVE: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: This…

DNA Methylation Description of Hippocampus, Cortex, Amygdala, and Blood of Drug-Resistant Temporal Lobe Epilepsy

Pubmed-Investigación

Mol Neurobiol. 2023 Apr;60(4):2070-2085. doi: 10.1007/s12035-022-03180-z. Epub 2023 Jan 5. ABSTRACT Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25-30% of epilepsy patients. The main objective is to simultaneously describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone…

Identification of Transporter Polymorphisms Influencing Metformin Pharmacokinetics in Healthy Volunteers

Pubmed-Investigación

J Pers Med. 2023 Mar 8;13(3):489. doi: 10.3390/jpm13030489. ABSTRACT For patients with type 2 diabetes, metformin is the most often recommended drug. However, there are substantial individual differences in the pharmacological response to metformin. To investigate the effect of transporter polymorphisms on metformin pharmacokinetics in an environment free of confounding variables, we conducted our study…

APRIL: A double-blind, placebo-controlled, randomized, Phase Ib/IIa clinical study of ApTOLL for the treatment of acute ischemic stroke

Pubmed-Investigación

Front Neurol. 2023 Feb 24;14:1127585. doi: 10.3389/fneur.2023.1127585. eCollection 2023. ABSTRACT In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect…

Impact of polymorphisms in CYP and UGT enzymes and ABC and SLCO1B1 transporters on the pharmacokinetics and safety of desvenlafaxine

Pubmed-Investigación

Front Pharmacol. 2023 Feb 2;14:1110460. doi: 10.3389/fphar.2023.1110460. eCollection 2023. ABSTRACT Venlafaxine pharmacokinetic variability and pharmacotherapy outcomes are well known to be related to CYP2D6 pharmacogenetic phenotype. In contrast, scarce pharmacogenetic information is available nowadays concerning desvenlafaxine, its active metabolite first marketed in 2012. The aim of this study was to evaluate the impact of 29…

Alternative Pharmacokinetic Metrics in Single-Dose Studies to Ensure Bioequivalence of Prolonged-Release Products at Steady State-A Case Study

Pubmed-Investigación

Pharmaceutics. 2023 Jan 26;15(2):409. doi: 10.3390/pharmaceutics15020409. ABSTRACT (1) Background: this article investigates which PK metrics in a single-dose study (concentration at the end of posology interval, Cτ, partial areas under the curve, pAUCs, or half-value duration, HVD) are more sensitive and less variable for predicting the failure of a prolonged-release product at steady-state that was…

Genetic Variation in CYP2D6 and SLC22A1 Affects Amlodipine Pharmacokinetics and Safety

Pubmed-Investigación

Pharmaceutics. 2023 Jan 25;15(2):404. doi: 10.3390/pharmaceutics15020404. ABSTRACT Amlodipine is an antihypertensive drug with unknown pharmacogenetic biomarkers. This research is a candidate gene study that looked for associations between amlodipine pharmacokinetics and safety and pharmacogenes. Pharmacokinetic and safety data were taken from 160 volunteers from eight bioequivalence trials. In the exploratory step, 70 volunteers were genotyped…

Dasatinib-induced spleen contraction leads to transient lymphocytosis

Pubmed-Investigación

Blood Adv. 2022 Dec 30:bloodadvances.2022009279. doi: 10.1182/bloodadvances.2022009279. Online ahead of print. ABSTRACT The tyrosine kinase inhibitor dasatinib is approved for Philadelphia chromosome positive leukemia, including chronic myeloid leukemia (CML). While effective and well tolerated, patients typically exhibit a transient lymphocytosis following dasatinib uptake. The underlying physiological process linking dasatinib to lymphocytosis has remained unknown to…