Molecular Design

MARCH 31, 2019

Controllability of exposure is the focus of pharmacokinetic optimization and I recently became aware of an exciting new development that will surely reshape the pharmacokinetic field and transform drug discovery beyond all recognition.

Pharmacokinetics 52

Pharmacokinetics Treatment Drugs 52

ASPET

JULY 15, 2024

Mathematical modeling combining pharmacokinetics (PK) and toxicodynamics (TD) is a promising approach for optimizing dosing strategies and reducing toxicity. XELOX therapy, which comprises capecitabine and oxaliplatin, is the standard first-line chemotherapeutic regimen for colorectal cancer.

Pharmacokinetics 100

Pharmacokinetics Therapies Drugs Treatment 100

ASPET

MAY 22, 2024

In this review, we will examine what is currently known about CBC with regards to pharmacodynamics, pharmacokinetics, and receptor profile. While the cannabinoids share a common precursor molecule, cannabigerol, they are structurally and pharmacologically unique. These differences may engender differing therapeutic potentials.

Pharmacokinetics 185

Pharmacokinetics Disease Production Research 185

Covalent Modifiers

AUGUST 4, 2024

Human volume of distribution (Vd) was well predicted using allometric scaling of animal pharmacokinetic data; the most reliable results were achieved using simple allometric scaling of unbound Vd values. These results provide a quantitative framework to guide appropriate method selection for human PK prediction with covalent drugs.

Pharmacokinetics 56

Pharmacokinetics Metabolic Stability Drugs 56

Alta Sciences

AUGUST 16, 2023

Microsampling for Pediatric Baricitinib Pharmacokinetics shajjar Wed, 08/16/2023 - 19:06 Publication bio-2023-0044_3.pdf pdf Tags Bioanalysis Category Journal Article Weight 1

Pharmacokinetics 40

Pharmacokinetics 40

Alta Sciences

AUGUST 22, 2023

34 — Toxicokinetics, Pharmacokinetics, and Pharmacodynamics mecabana Tue, 08/22/2023 - 17:31 Publication the-altascientist-issue-34-toxicokinetics-pharmacokinetics-and-pharmacodynamics.pdf URL [link] Weight 1 Tags Research Support

Pharmacokinetics 40

Pharmacokinetics Research 40

Alta Sciences

AUGUST 22, 2023

34 — TOXICOKINETICS, PHARMACOKINETICS, AND PHARMACODYNAMICS mecabana Tue, 08/22/2023 - 17:31 Publication the-altascientist-issue-34-toxicokinetics-pharmacokinetics-and-pharmacodynamics.pdf URL [link] Weight 1 Tags Manufacturing and Analytical Services

Pharmacokinetics 40

Pharmacokinetics 40

ASPET

SEPTEMBER 28, 2023

These protocols were then used to determine the plasma pharmacokinetics of agmatine and the extent of distribution to the CNS. Upon application of this protocol to pharmacokinetic study, IV agmatine showed a half-life in plasma ranging between 18.9 The protocol also adequately withstood stability and dilution conditions.

Pharmacokinetics 100

Pharmacokinetics FDA Therapies Drugs 100

ASPET

AUGUST 8, 2024

Lenacapavir (LEN), a long-acting injectable, is the first approved human immunodeficiency virus type 1 capsid inhibitor and one of a few FDA-approved drugs that exhibit atropisomerism.

Pharmacogenetics 100

Pharmacogenetics Pharmacokinetics FDA Approval Virus 100

ASPET

JUNE 27, 2024

Furthermore, we evaluated the in vivo pharmacokinetics of the analogs following single dose IV and oral administration. Surprisingly, and at odds with their pharmacokinetic and in vitro human activity data, most analogs potently induced uterotrophic effects in estrogen-naïve female mice.

Pharmacokinetics 100

Pharmacokinetics Drug Development Disease Drugs 100

Drug Patent Watch

OCTOBER 30, 2023

Over the past two decades, Bayer Pharma has developed an in silico absorption, distribution, metabolism, and excretion (ADMET) platform with the aim of generating models for various pharmacokinetic and physicochemical… The post Advancements in In Silico ADMET Modeling: A 20-Year Journey of Machine Learning in Drug Discovery at Bayer Pharma appeared (..)

Pharmacokinetics 111

Pharmacokinetics Drugs 111

ASPET

SEPTEMBER 12, 2023

This first-in-human, randomized, double-blind, placebo-controlled study (NCT04497662) evaluated safety, pharmacokinetics, receptor occupancy, and pharmacodynamics of the humanized anti-CD40 monoclonal antibody KPL-404. Nonlinear dose-dependent changes in various pharmacokinetic parameters were identified following the range of IV doses.

Pharmacokinetics 100

Pharmacokinetics Immune Response Trials Clinical Trials 100

ASPET

SEPTEMBER 16, 2024

Acknowledging the potential for inter-species differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited.

Pharmacogenetics 100

Pharmacogenetics DNA Treatment Pharmacokinetics 100

ASPET

SEPTEMBER 7, 2023

The DDI covered in this review include pharmacokinetic DDI arising from enzyme inhibition or induction, primarily due to inhibition of cytochrome p450 enzymes (CYPs). This review focuses on the current knowledge of common opioid drug-drug interactions (DDI), focusing specifically on hydrocodone, oxycodone, and morphine DDI.

Pharmacokinetics 100

Pharmacokinetics Drugs Treatment Disease 100

ASPET

SEPTEMBER 16, 2024

PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor (TGFβRIi) with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species.

Pharmacokinetics 100

Pharmacokinetics Packaging Drugs 100

Chemical Biology and Drug Design

DECEMBER 5, 2024

The synthesized molecules were assessed for their pharmacological potential via cell viability, drug metabolism and pharmacokinetics (DMPK), and MERTK inhibition studies corroborated by in silico studies. The molecules were synthesized via a multi-step synthetic approach.

Immune Response 100

Immune Response Pharmacokinetics Regulations Treatment 100

ASPET

OCTOBER 24, 2023

The pharmacokinetic and pharmacodynamic properties of orally administered BBP-671 evaluated in cannulated rats showed that CoA concentrations were elevated in blood, liver and brain. This work describes the pharmacokinetic/pharmacodynamic properties of BBP-671, a pantothenate kinase activator.

Metabolic Stability 100

Metabolic Stability Pharmacokinetics Regulations Treatment 100

Broad Institute

JULY 17, 2024

Together, the tools estimate how a drug may impact diverse outcomes of interest to drug developers: general cellular health, pharmacokinetics, and heart and liver function. Drug developers also assess pharmacokinetic effects, or how an organism absorbs, distributes, metabolizes, and clears a drug.

Pharmacokinetics 84

Pharmacokinetics Molecular Biology Drugs FDA 84

SCIENMAG: Medicine & Health

NOVEMBER 1, 2023

A small clinical trial with a pharmacokinetic sub-study, led by a world-renowned pharmacologist at the University of Houston, has demonstrated the promising effectiveness of the drug Riluzole for improving functionality in people with acute spinal cord injuries (SCI) if the drug is taken within 12 hours post-injury.

Clinical Trials 86

Clinical Trials Trials Pharmacokinetics Drugs 86

Chemical Biology and Drug Design

JANUARY 29, 2024

In-silico ADME studies significant values of pharmacokinetic parameters and demonstrated good drug like characteristics based on Lipinski's rule of five. In addition, the QSTR study of new compounds were carried out with the help of Toxicity Estimation Software Tool (T.E.S.T). The results showed slight toxic nature of new compounds.

Pharmacokinetics 100

Pharmacokinetics Production Drugs Research 100

Chemical Biology and Drug Design

AUGUST 18, 2024

The drug-like properties (like pharmacokinetics and pharmacodynamics) of the individual scaffolds can be improved by benzimidazole–oxadiazole chimeric molecules via a molecular hybridisation approach. Benzimidazole and oxadiazole cores can either be fused or incorporated using either functional groups/bonds.

Pharmacokinetics 100

Pharmacokinetics Drugs Research 100

Chemical Biology and Drug Design

MARCH 7, 2024

The physicochemical, pharmacokinetic, drug-like, and drug-score features of all synthesized compounds were assessed using the online Swiss ADME and Protein Plus software. AutoDock 4.2 was used for their in silico screening against AMPA (-amino-3-hydroxy-5-methylisoxazole) receptor (PDB ID:3m3f). kJ/mol, respectively.

Pharmacokinetics 100

Pharmacokinetics Drugs Research 100

Alta Sciences

JUNE 24, 2023

Design and Validation of a Bioanalytical Method to Support a Clinical Pharmacokinetic Study Involving the Use of Multiple Lots of the Biological Therapeutic Drug lperez Sat, 06/24/2023 - 08:07 Publication Altasciences_WRIB_2023_Design_and_Validation_of_a_Bioanalytical_Method_to_Support_a_Clinical_Pharmacokinetic_Study.pdf Tags Bioanalysis Date of publication (..)

Pharmacokinetics 40

Pharmacokinetics Drugs 40

The Pharma Data

NOVEMBER 17, 2020

The study demonstrated favorable proof-of-concept for LYT-100’s tolerability and pharmacokinetic (PK) profile, which will also enable twice-a-day (BID) dosing of LYT-100 in future studies.

Pharmacokinetics 52

Pharmacokinetics Treatment Trials Production 52

Broad Institute

OCTOBER 29, 2024

So the team turned their attention to optimizing the pharmacokinetic profile of BRD-810 to preserve its ability to kill tumor cells without negatively affecting heart cells.

Drugs 133

Drugs Small Molecule Pharmacokinetics Clinical Trials 133

ASPET

OCTOBER 23, 2024

Neither nimodipine nor NP10679 alter each other's pharmacokinetic profile, suggesting no obvious drug-drug interactions. We found that NP10679 produced durable improvement of behavioral deficits in a well-characterized murine model of SAH, and these effects were greater than those produced by nimodipine alone, the current standard of care.

Clinical Development 100

Clinical Development Treatment Pharmacokinetics Drugs 100

ASPET

JUNE 27, 2024

Secondary VAS and pharmacokinetic (PK) endpoints and adverse events were assessed. Three doses of lenabasum (20, 60, and 120mg) were compared to placebo, and nabilone (3 and 6mg). The primary endpoint was the peak effect (Emax) on a bipolar Drug Liking visual analog scale (VAS). Results : Lenabasum was safe and well tolerated.

FDA Approval 100

FDA Approval Pharmacokinetics FDA Disease 100

Chemical Biology and Drug Design

MARCH 5, 2024

The potent compounds 5d , 5e , and 5f were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM. In addition to this, molecular docking studies of compounds 5d , 5e , and 5f demonstrated that these compounds had more EGFR-binding interactions.

Pharmacokinetics 100

Pharmacokinetics Drugs Research 100

Chemical Biology and Drug Design

MAY 31, 2023

Finally, in silico results and pharmacokinetic parameters of ADME showed that these compounds have good oral bioavailability properties. According to the docking result, the most stable conformation of AChE and compound 3i showed that it has a binding affinity of −10.82 kcal/moL.

Pharmacokinetics 100

Pharmacokinetics Research 100

ASPET

SEPTEMBER 16, 2024

Here, we describe 8015-P2, a new small molecule mitofusin activator with ~10-fold greater potency and improved in vivo pharmacokinetics vs comparators, and demonstrate its rapid reversal of sensory and motor neuron dysfunction in an Mfn2 T105M knock-in mouse model of Charcot-Marie-Tooth disease type 2A.

Small Molecule 100

Small Molecule Pharmacokinetics Engineering Disease 100

ASPET

AUGUST 5, 2024

The data obtained can be used in the future to predict transporter-mediated drug clearance changes during inflammation through physiologically-based pharmacokinetic modeling and simulation.

Pharmacogenetics 100

Pharmacogenetics Pharmacokinetics Drugs 100

ASPET

APRIL 26, 2024

In this study, we investigated the systemic pharmacokinetics and subsequent CNS distribution of two potent HDACIs, vorinostat and quisinostat, in the murine model. Although many HDACIs have shown potential in in vitro studies, they have had modest efficacy in vivo.

Pharmacogenetics 100

Pharmacogenetics Pharmacokinetics Clinical Trials Trials 100

ASPET

JANUARY 31, 2024

The effects of BMS-986371, a potent in vitro inhibitor of BCRP ( IC 50 0.40 µM), on the pharmacokinetics of riboflavin, isobutyryl carnitine, and arginine were then examined in healthy male adults (N = 14 or 16) following oral administration of methotrexate (MTX) (7.5

Pharmacogenetics 100

Pharmacogenetics Pharmacokinetics Drug Development Drugs 100

ASPET

JANUARY 22, 2024

The pharmacokinetics was measured by LC-MS/MS analysis. We investigated the physiological effect of a novel NF-kB inhibitory compound, 1 H -pyrazolo[3,4- d ]pyrimidin-4-amine derivative (INH #1) on three inflammatory animal models.

Immune Response 100

Immune Response Pharmacokinetics Production Drugs 100

ASPET

AUGUST 10, 2023

Pharmacokinetic half-lives ranged from 55 to 100 hours over the clinically relevant dose range, consistent with the expected half-life extension by glycoPEGylation. These findings provide evidence that pegozafermin is a promising candidate molecule for the treatment of patients with NASH or SHTG.

Cell Based Assays 100

Cell Based Assays Pharmacokinetics Regulations Treatment 100

ASPET

AUGUST 21, 2024

This review details the onset mechanisms of drug-induced TdP, including I Kr inhibition, pharmacokinetic factors, autonomic regulation and reduced repolarization reserve. It also explores the utility of proarrhythmic surrogate markers (J-T peak , T peak -T end and terminal repolarization period) besides QT interval.

Compliance 100

Compliance Pharmacokinetics Drugs Engineering 100

Chemical Biology and Drug Design

MARCH 6, 2024

Thus, polonilignan has been identified as a new pan-cytokine and NO inhibitor, it is recommended to optimise a method for the synthesis of this small molecular weight lignan and explore its pharmacokinetic characteristics, toxicity and therapeutic effect under various chronic inflammatory disease models.

Pharmacokinetics 100

Pharmacokinetics Regulations Disease Production 100