Drugs, Pharmacogenetics and Pharmacokinetics

Pharmacokinetics of panobinostat: Inter-species difference in metabolic stability [Metabolism, Transport, and Pharmacogenetics]

ASPET

FEBRUARY 26, 2024

The objective of this study was to examine the in vitro metabolic stability of panobinostat in different matrices and assess the influence of that metabolic stability on the in vivo pharmacokinetics and CNS delivery of panobinostat.

Metabolic Stability

Metabolic Stability Pharmacokinetics Pharmacogenetics Treatment

Preclinical systemic pharmacokinetics, dose-proportionality, and CNS distribution of the ATM inhibitor WSD0628, a novel radiosensitizer for the treatment of brain tumors [Metabolism, Transport, and Pharmacogenetics]

ASPET

JUNE 10, 2024

Efficacy of radiosensitizers for brain tumors may be influenced by a lack of effective drug delivery across the blood-brain barrier (BBB). The objective of this study was to evaluate the systemic pharmacokinetics and mechanisms that influence the CNS distribution of WSD0628, a novel and potent ATM inhibitor, in the mouse.

Pharmacokinetics

Pharmacokinetics Pharmacogenetics Treatment DNA

An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction: Application of In Vitro Assays and Physiologically Based Pharmacokinetic Models to Understand Clinical Observations [Metabolism, Transport, and Pharmacogenetics]

ASPET

AUGUST 4, 2023

The objective of this study was to mechanistically assess the pharmacokinetic goldenseal-midazolam interaction using an integrated in vitro - in vivo - in silico approach. min -1 , respectively). The objective of the current work was to evaluate fundamental mechanisms underlying the clinically observed goldenseal-midazolam interaction.

Pharmacokinetics

Pharmacokinetics Pharmacogenetics Production Drugs

Webinars

From Diagnosis to Delivery: How AI is Revolutionizing the Patient Experience

MORE WEBINARS

Dysregulation of Human Hepatic Drug Transporters by Proinflammatory Cytokines [Metabolism, Transport, and Pharmacogenetics]

ASPET

AUGUST 5, 2024

Proinflammatory cytokines, elevated during inflammation caused by infection and/or autoimmune disorders, result in reduced clearance of drugs eliminated primarily by cytochrome P450 enzymes (CYPs). However, the effect of cytokines on hepatic drug transporter expression or activity has not been well-studied. or 1 ng/mL).

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Drugs

Lenacapavir Exhibits Atropisomerism - Mechanistic Pharmacokinetics and Disposition Studies of Lenacapavir Reveal Intestinal Excretion as a Major Clearance Pathway [Metabolism, Transport, and Pharmacogenetics]

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. The volume of distribution was moderate in nonclinical species and consistent with the tissue distribution observed by whole body autoradiography in rats.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics FDA Approval Virus

Factors influencing the Central Nervous System (CNS) distribution of the ATR inhibitor elimusertib (BAY1895344): Implications for the treatment of CNS tumors [Metabolism, Transport, and Pharmacogenetics]

ASPET

SEPTEMBER 16, 2024

GBM has a poor prognosis despite aggressive treatment, in part due to lack of adequate drug permeability at the BBB. CNS distribution of elimusertib is partially limited by P-gp efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain.

Pharmacogenetics

Pharmacogenetics DNA Pharmacokinetics Treatment

Central Nervous System Distributional Kinetics of Selected Histone Deacetylase Inhibitors [Metabolism, Transport, and Pharmacogenetics]

ASPET

APRIL 26, 2024

This lack of activity could be due to insufficient CNS exposure to the unbound drug. In this study, we investigated the systemic pharmacokinetics and subsequent CNS distribution of two potent HDACIs, vorinostat and quisinostat, in the murine model.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Clinical Trials Trials

A Pilot Study to Assess the Suitability of Riboflavin as A Surrogate Marker of Breast Cancer Resistance Protein (BCRP) in Healthy Participants [Metabolism, Transport, and Pharmacogenetics]

ASPET

JANUARY 31, 2024

First, we assessed the substrate potential of riboflavin towards other major drug transporters using established transfected cell systems. Overall, these data indicate that plasma riboflavin is a promising biomarker of BCRP that may offer a possibility to assess drug candidate as a BCRP modulator in early drug development.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Drug Development Drugs

Significance of organic anion transporter 2 and organic cation transporter 2 in creatinine clearance: Mechanistic evaluation using freshly-prepared human primary renal proximal tubule cells [Metabolism, Transport, and Pharmacogenetics]

ASPET

NOVEMBER 17, 2023

Quantitative pharmacokinetic models should therefore focus on OCT2/MATE when describing serum creatinine and creatinine clearance modulation by inhibitor drugs and genotype- or disease-related activity changes.

Pharmacogenetics

Pharmacogenetics Pharmacokinetics Disease Drugs

Drug Discovery Digest

Pharmacokinetics of panobinostat: Inter-species difference in metabolic stability [Metabolism, Transport, and Pharmacogenetics]

Preclinical systemic pharmacokinetics, dose-proportionality, and CNS distribution of the ATM inhibitor WSD0628, a novel radiosensitizer for the treatment of brain tumors [Metabolism, Transport, and Pharmacogenetics]

An Integrative Approach to Elucidate Mechanisms Underlying the Pharmacokinetic Goldenseal-Midazolam Interaction: Application of In Vitro Assays and Physiologically Based Pharmacokinetic Models to Understand Clinical Observations [Metabolism, Transport, and Pharmacogenetics]

Webinars

Dysregulation of Human Hepatic Drug Transporters by Proinflammatory Cytokines [Metabolism, Transport, and Pharmacogenetics]

Lenacapavir Exhibits Atropisomerism - Mechanistic Pharmacokinetics and Disposition Studies of Lenacapavir Reveal Intestinal Excretion as a Major Clearance Pathway [Metabolism, Transport, and Pharmacogenetics]

Factors influencing the Central Nervous System (CNS) distribution of the ATR inhibitor elimusertib (BAY1895344): Implications for the treatment of CNS tumors [Metabolism, Transport, and Pharmacogenetics]

Central Nervous System Distributional Kinetics of Selected Histone Deacetylase Inhibitors [Metabolism, Transport, and Pharmacogenetics]

A Pilot Study to Assess the Suitability of Riboflavin as A Surrogate Marker of Breast Cancer Resistance Protein (BCRP) in Healthy Participants [Metabolism, Transport, and Pharmacogenetics]

Significance of organic anion transporter 2 and organic cation transporter 2 in creatinine clearance: Mechanistic evaluation using freshly-prepared human primary renal proximal tubule cells [Metabolism, Transport, and Pharmacogenetics]

Stay Connected