Influence of nonspecific brain and plasma binding on CNS exposure: implications for rational drug discovery

J Cory Kalvass, TS Maurer - Biopharmaceutics & drug …, 2002 - Wiley Online Library
Relative plasma, brain and cerebrospinal fluid (CSF) exposures and unbound fractions in
plasma and brain were examined for 18 proprietary compounds in rats. The relationship …

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, …

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 …

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 KalvassJ. Cory Kalvass was supported by a predoctoral fellowship in
pharmacokinetics and drug disposition from the Eli Lilly and Company Foundation. …

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
P-glycoprotein (P-gp) is expressed at the blood-brain barrier (BBB) and restricts the penetration
of its substrates into the central nervous system (CNS). In vitro substrate assessment for …

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 …

Multiple mechanisms are involved in the biliary excretion of acetaminophen sulfate in the rat: role of Mrp2 and Bcrp1

…, LO Webster, AS Bridges, JC Kalvass… - Drug metabolism and …, 2005 - ASPET
Previous reports have demonstrated that sulfate metabolites may be excreted into bile by
the multidrug resistance-associated protein 2 (Mrp2, Abcc2). Although recombinant human …