Estimated time of arrival and debiasing the time saving bias.

The time saving bias predicts that the time saved when increasing speed from a high speed is overestimated, and underestimated when increasing speed from a slow speed. In a questionnaire, time saving judgements were investigated when information of estimated time to arrival was provided. In an active driving task, an alternative meter indicating the inverted speed was used to debias judgements.

Isoniazid mediates the CYP2B6*6 genotype-dependent interaction between efavirenz and antituberculosis drug therapy through mechanism-based inactivation of CYP2A6.

Efavirenz is commonly used to treat patients coinfected with human immunodeficiency virus and tuberculosis. Previous clinical studies have observed paradoxically elevated efavirenz plasma concentrations in patients with the CYP2B6*6/*6 genotype (but not the CYP2B6*1/*1 genotype) during coadministration with the commonly used four-drug antituberculosis therapy. This study sought to elucidate the mechanism underlying this genotype-dependent drug-drug interaction.

Characterization of recombinant human carboxylesterases: fluorescein diacetate as a probe substrate for human carboxylesterase 2.

Human carboxylesterase (CES) 1 and CES2 are members of the serine hydrolase superfamily, and both exhibit broad substrate specificity and are involved in xenobiotic and endobiotic metabolism. Although expression of CES1 and CES2 occurs in several organs, their expression in liver and small intestine is predominantly attributed to CES1 and CES2, respectively. We successfully expressed CES1 form b (CES1-b) and form c (CES1-c) as well as CES2 in baculovirus-infected High Five insect cells.

CYP4F enzymes are responsible for the elimination of fingolimod (FTY720), a novel treatment of relapsing multiple sclerosis.

Fingolimod (FTY720, Gilenya, 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol) is a novel drug recently approved in the United States for the oral treatment of relapsing multiple sclerosis. The compound is eliminated predominantly by ω-hydroxylation, followed by further oxidation. The ω-hydroxylation was the major metabolic pathway in human liver microsomes (HLM).

Driver experience and cognitive workload in different traffic environments.

How do levels of cognitive workload differ between experienced and inexperienced drivers? In this study we explored cognitive workload and driver experience, using a secondary task method, the peripheral detection task (PDT) in a field study. The main results showed a large and statistically significant difference in cognitive workload levels between experienced and inexperienced drivers. Inexperienced, low mileage drivers had on average approximately 250 milliseconds (ms) longer reaction times to a peripheral stimulus, than the experienced drivers.

New technologies for assessing UDP-glucuronosyltransferase (UGT) metabolism in drug discovery and development.

UDP-glucuronosyltransferases (UGT) are important hepatic xenobiotic metabolizing enzymes. As with the cytochrome P450 class of enzymes, a multiplicity of UGT forms exists in human liver and extra-hepatic tissues. The lack of a comprehensive set of UGT-selective antibodies, substrates and inhibitors has limited the scope of studies that can be conducted with human liver preparations.

In vitro inhibition of UDP glucuronosyltransferases by atazanavir and other HIV protease inhibitors and the relationship of this property to in vivo bilirubin glucuronidation.

Several human immunodeficiency virus (HIV) protease inhibitors, including atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir, were tested for their potential to inhibit uridine 5'-diphospho-glucuronosyltransferase (UGT) activity. Experiments were performed with human cDNA-expressed enzymes (UGT1A1, 1A3, 1A4, 1A6, 1A9, and 2B7) as well as human liver microsomes. All of the protease inhibitors tested were inhibitors of UGT1A1, UGT1A3, and UGT1A4 with IC(50) values that ranged from 2 to 87 microM.

Using mobile telephones: cognitive workload and attention resource allocation.

Driver distraction is recognized as being one of the central causes of road traffic incidents and mobile telephones are tangible devices (among many other electronic devices) that can distract the driver through changes in workload. Forty participants completed a motorway route characterized by a low level of road complexity in the form of vehicle handling and information processing. A peripheral detection task (PDT) was employed to gauge mental workload.

Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible.

Azamulin [14-O-(5-(2-amino-1,3,4-triazolyl)thioacetyl)-dihydromutilin] is an azole derivative of the pleuromutilin class of antiinfectives. We tested the inhibition potency of azamulin toward 18 cytochromes P450 using human liver microsomes or microsomes from insect cells expressing single isoforms. In a competitive inhibition model, IC(50) values for CYP3A (0.

Evaluation of 3'-azido-3'-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism.

UDP-glucuronosyltransferase 2B7 (UGT2B7) is involved in the glucuronidation of a wide array of clinically important drugs and endogenous compounds in humans. The aim of this study was to identify an isoform-selective probe substrate that could be used to investigate genetic and environmental influences on glucuronidation mediated by UGT2B7. Three potential probe substrates [3'-azido-3'-deoxythymidine (AZT), morphine, and codeine], were evaluated using recombinant UGTs and human liver microsomes (HLMs; n = 54).

Assessing pregnancy risks of azole antifungals using a high throughput aromatase inhibition assay.

Unlabelled: Human aromatase (CYP19) converts C19 androgens to aromatic C18 estrogenic steroids. Its activity is critical for early and mid pregnancy maintenance and in regulating parturition in late pregnancy. Past studies have utilized placental microsome tritiated water release assay to assess drug-hormone interactions with estrogen synthesis.