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St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor.
TLDR
It is shown that hyperforin, a constituent of St. John's wort with antidepressant activity, is a potent ligand for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the cytochrome P450 (CYP) 3A4 monooxygenase. Expand
Passive Permeability and P-Glycoprotein-Mediated Efflux Differentiate Central Nervous System (CNS) and Non-CNS Marketed Drugs
TLDR
This study on a large, diverse set of marketed compounds clearly demonstrates that permeability, Pgp-mediated efflux, and certain physicochemical properties are factors that differentiate CNS and non-CNS drugs. Expand
The Role of Efflux and Uptake Transporters in N-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, Lapatinib) Disposition and
TLDR
In vitro and in vivo preclinical investigations provide a mechanistic basis for elucidating clinical drug interactions and demonstrated that brain concentrations of lapatinib were low and influenced by efflux transporters at the blood-brain barrier. Expand
IN VITRO P-GLYCOPROTEIN INHIBITION ASSAYS FOR ASSESSMENT OF CLINICAL DRUG INTERACTION POTENTIAL OF NEW DRUG CANDIDATES: A RECOMMENDATION FOR PROBE SUBSTRATES
TLDR
It is recommended that digoxin be considered as the standard in vitro probe to investigate the inhibition profiles of new drug candidates and shows that it may not be necessary to generate IC50 values with multiple probe substrates for Pgp as is currently done for cytochrome P450 3A4. Expand
P-glycoprotein influences the brain concentrations of cetirizine (Zyrtec), a second-generation non-sedating antihistamine.
TLDR
It is demonstrated that Pgp-mediated efflux and passive permeability contribute to the low cetirizine brain concentrations in mice and that these properties account for the differences in the sedation side-effect profiles of cetIRizine and hydroxyzine. Expand
CYP3A4 expressed by insect cells infected with a recombinant baculovirus containing both CYP3A4 and human NADPH-cytochrome P450 reductase is catalytically similar to human liver microsomal CYP3A4.
TLDR
Recombinant CYP3A4-OR was catalytically similar to human liver CYP2A4 based on similarities in the testosterone metabolite profile, time course of metabolite formation, Vmax and Km values and the degree of P450 activation in the presence of 20 microM 7,8-benzoflavone. Expand
Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans.
TLDR
It is concluded that ondansetron is metabolized by multiple forms of cytochrome P450, and this limits the likelihood of a clinically relevant interaction with ondANSetron by a modulator of a single form of cy tochrome P 450. Expand
In vitro absorption and secretory quotients: practical criteria derived from a study of 331 compounds to assess for the impact of P-glycoprotein-mediated efflux on drug candidates.
TLDR
This study demonstrates that the optimal AQ and SQ value to classify compounds as Pgp substrates was 0.3 and provides a basis to deploy unidirectional efflux assays in the early stages of drug discovery, which would benefit from the twofold increase in throughput over current bidirectional transport assays. Expand
The rabbit pulmonary monooxygenase system. Immunochemical and biochemical characterization of enzyme components.
TLDR
Pulmonary and hepatic NADPH-cytochrome P-450 reductases also have identical physical, catalytic, and immunochemical properties, and the lack of response of the rabbit pulmonary monooxygenase system to phenobarbital is apparently not due to an inability of the lung to synthesize the enzymes induced by phenobarBital in the liver. Expand
The relationship between increases in the hepatic content of cytochrome P-450, form 5, and in the metabolism of aromatic amines to mutagenic products following treatment of rabbits with phenobarbital.
TLDR
The results indicate that phenobarbital increases the hepatic microsomal concentration of cytochrome P-450, form 5, to the same extent that it increases form 5-mediated metabolism of aromatic amines to mutagenic products: 10- to 12-fold. Expand
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