Why clinical modulation of efflux transport at the human blood–brain barrier is unlikely: the ITC evidence‐based position

JC Kalvass, JW Polli, DL Bourdet… - Clinical …, 2013 - Wiley Online Library
Drug interactions due to efflux transport inhibition at the blood–brain barrier (BBB) have
been receiving increasing scrutiny because of the theoretical possibility of adverse central …

ITC recommendations for transporter kinetic parameter estimation and translational modeling of transport‐mediated PK and DDIs in humans

…, T Ishikawa, M Jamei, JC Kalvass… - Clinical …, 2013 - Wiley Online Library
This white paper provides a critical analysis of methods for estimating transporter kinetics
and recommendations on proper parameter calculation in various experimental systems. …

Industry perspective on contemporary protein-binding methodologies: considerations for regulatory drug-drug interaction and related guidelines on highly bound …

…, R Fricke, A Ghosh, P Harradine, JC Kalvass… - Journal of …, 2017 - Elsevier
Regulatory agencies have recently issued drug-drug interaction guidelines, which require
determination of plasma protein binding (PPB). To err on the conservative side, the agencies …

Use of plasma and brain unbound fractions to assess the extent of brain distribution of 34 drugs: comparison of unbound concentration ratios to in vivo p-glycoprotein …

JC Kalvass, TS Maurer, GM Pollack - Drug metabolism and disposition, 2007 - ASPET
The P-glycoprotein (P-gp)-deficient mouse model is used to assess the influence of P-gp-mediated
efflux on the central nervous system (CNS) distribution of drugs. The steady-state …

In vivo activation of human pregnane X receptor tightens the blood-brain barrier to methadone through P-glycoprotein up-regulation

…, AMS Hartz, ER Olson, R Zhao, JC Kalvass… - Molecular …, 2006 - ASPET
The ATP-driven drug export pump, P-glycoprotein, is a primary gatekeeper of the blood-brain
barrier and a major impediment to central nervous system (CNS) pharmacotherapy. …

Pharmacokinetics and pharmacodynamics of seven opioids in P-glycoprotein-competent mice: assessment of unbound brain EC50, u and correlation of in vitro …

JC Kalvass, ER Olson, MP Cassidy, DE Selley… - … of Pharmacology and …, 2007 - ASPET
This study was conducted to assess the utility of unbound brain EC 50 (EC 50,u ) as a measure
of in vivo potency for centrally active drugs. Seven μ-opioid agonists (alfentanil, fentanyl, …

The important role of Bcrp (Abcg2) in the biliary excretion of sulfate and glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in mice

…, K Nezasa, X Tian, JC Kalvass… - Molecular …, 2006 - ASPET
The role of Mrp2, Bcrp, and P-glycoprotein in the biliary excretion of acetaminophen sulfate (AS)
and glucuronide (AG), 4-methylumbelliferyl sulfate (4MUS) and glucuronide (4MUG), …

Kinetic considerations for the quantitative assessment of efflux activity and inhibition: implications for understanding and predicting the effects of efflux inhibition

JC Kalvass, GM Pollack - Pharmaceutical research, 2007 - Springer
… Cory Kalvass … Cory Kalvass was supported by a predoctoral fellowship in pharmacokinetics
and drug disposition from the Eli Lilly and Company Foundation. … Cory Kalvass

In vitro P-glycoprotein efflux ratio can predict the in vivo brain penetration regardless of biopharmaceutics drug disposition classification system class

R Kikuchi, SM de Morais, JC Kalvass - Drug Metabolism and Disposition, 2013 - ASPET
… Indeed, Kalvass and coworkers previously proposed that brain impairment, ie, [plasma] u
/[brain] u , being greater than 3, or in other words, unbound brain/plasma ratio less than 0.33, is …

Relationship between drug/metabolite exposure and impairment of excretory transport function

MJ Zamek-Gliszczynski, JC Kalvass, GM Pollack… - Drug Metabolism and …, 2009 - ASPET
The quantitative impact of excretory transport modulation on the systemic exposure to
xenobiotics and derived metabolites is poorly understood. This article presents fundamental …