1β-Hydroxydeoxycholic acid as an endogenous biomarker in human plasma for assessment of drug-drug interaction with moderate CYP3A inhibitor.

1β-Hydroxydeoxycholic acid (1β-OH DCA) in plasma has been shown to be a promising biomarker to assess drug-drug interaction (DDI) with a strong CYP3A inducer or a strong CYP3A inhibitor. The changes in total 1β-OH DCA (sum of 1β-OH DCA, 1β-OH glycine deoxycholic acid, and 1β-OH taurine deoxycholic acid equivalents) were more significant than those observed from 4β-hydroxycholesterol, which has been limited to the identification of CYP3A inducers, not CYP3A inhibitors. The significant reduction in total 1β-OH DCA in response to strong CYP3A inhibitors led us to further explore its utility as a biomarker for DDI with moderate CYP3A inhibitors.

Emerging applications of quantitative supercritical fluid chromatography-tandem mass spectrometry for chiral bioanalysis.

Individual stereoisomers of a chiral drug can possess different pharmacokinetic (PK)/pharmacodynamic (PD) properties, leading to different therapeutic/toxicological effects. Therefore, chiral bioanalytical methods are required for individual stereoisomers to assess their PK properties and potential chiral inversion in vivo. Supercritical fluid chromatography (SFC) has not been a mainstay in bioanalytical labs due to limitations of robustness/reliability of old generations of SFC instrumentation.

1β-Hydroxydeoxycholic Acid as an Endogenous Biomarker in Human Plasma for Assessment of CYP3A Clinical Drug-Drug Interaction Potential.

4-Hydroxycholesterol (4-HC) in plasma has been used as a biomarker to assess CYP3A drug-drug interaction (DDI) potential during drug development. However, due to the long half-life and narrow dynamic range of 4-HC, its use has been limited to the identification of CYP3A inducers, but not CYP3A inhibitors. The formation of 1-hydroxydeoxycholic acid (1-OH DCA) from deoxycholic acid (DCA) is mediated by CYP3A, thus 1-OH DCA can potentially serve as an alternative to 4-HC for assessment of CYP3A DDI potential.

The "SuperAgers" construct in clinical practice: neuropsychological assessment of illiterate and educated elderly.

Introduction: The demographic transition is a global event intensified during the last decades that represents population aging. Thus, the studies directed to the elderly 80 years of age or more with preserved cognitive functions (named SuperAgers) emerges as a possible path to full comprehension of the health of those aging with acceptable levels of functionality and independency.

Objective: To evaluate the cognitive performance of the elderly over 80 years old, associating the results to their educational level.

Accuracy of praxis test from Cambridge Cognitive Examination (CAMCOG) for Alzheimer's disease: a cross-sectional study.

Background: Praxis impairment may be one of the first symptoms manifested in dementia, primarily in cortical dementia. The Cambridge Cognitive Examination (CAMCOG) evaluates praxis, but little is known about the accuracy of CAMCOG for diagnosing dementia. The aims here were to investigate the accuracy of praxis and its subitems in CAMCOG (constructive, ideomotor and ideational subitems) for diagnosing Alzheimer's disease (AD) among elderly patients.

Effects of Adjuvant Chemotherapy on Cognitive Function of Patients With Early-stage Colorectal Cancer.

Purpose: Chemotherapy-related cognitive impairment can occur in cancer survivors after treatment, especially those patients who have undergone chemotherapy for breast cancer. The frequency and to what extent such toxicity develops in colorectal cancer (CRC) survivors is unknown. The present prospective study evaluated the effects of adjuvant chemotherapy on the cognitive performance of patients with localized CRC compared with a control group who had not undergone chemotherapy.

Depression is associated with self-rated frailty in older adults from an outpatient clinic: a prospective study.

Unlabelled: ABSTRACTObjectives:The aim of the present study was to evaluate the association between depression and SSRI monotherapy and frailty both baseline and prospectively in older adults.

Design: Prospective cohort study, 12-month follow-up.

Setting: Geriatric outpatient clinic in São Paulo, Brazil.

Performance of the Pentagon Drawing test for the screening of older adults with Alzheimer's dementia.

Unlabelled: The Pentagon Drawing Test (PDT) is a common cognitive screening test.

Objective: The aim of this study was to evaluate performance properties of a specific PDT scoring scale in older adults with Alzheimer's disease (AD) and healthy controls.

Methods: A cross-sectional study of 390 elderly patients, aged 60 years or older with at least two years of education was conducted.

Use of 4β-hydroxycholesterol in animal and human plasma samples as a biomarker for CYP3A induction.

Background: 4β-hydroxycholesterol (4βHC) has recently been proposed as a potential endogenous biomarker for CYP3A activity. Developing bioanalytical assays for 4βHC is challenging for several reasons, including endogenous background levels in plasma; the presence of free and ester forms; the inherent lack of MS sensitivity; and the presence of multiple positional isomers.

Results: Bioanalytical assays in mouse, rat, dog and human plasma were adapted and modified from a previous published human plasma assay for 4βHC by using alkaline de-esterification, picolinic derivatization, a surrogate analyte (d7-4βHC) in authentic matrices and chromatographic conditions that showed good separation from isobaric, positional isomers.

An integrated bioanalytical method development and validation approach: case studies.

We proposed an integrated bioanalytical method development and validation approach: (1) method screening based on analyte's physicochemical properties and metabolism information to determine the most appropriate extraction/analysis conditions; (2) preliminary stability evaluation using both quality control and incurred samples to establish sample collection, storage and processing conditions; (3) mock validation to examine method accuracy and precision and incurred sample reproducibility; and (4) method validation to confirm the results obtained during method development. This integrated approach was applied to the determination of compound I in rat plasma and compound II in rat and dog plasma. The effectiveness of the approach was demonstrated by the superior quality of three method validations: (1) a zero run failure rate; (2) >93% of quality control results within 10% of nominal values; and (3) 99% incurred sample within 9.