Quantitative Expression of Hepatobiliary Transporters and Functional Uptake of Substrates in Hepatic Two-Dimensional Sandwich Cultures: A Comparative Evaluation of Upcyte and Primary Human Hepatocytes.

Deficient functional expression of drug transporters incapacitates most hepatic cell lines as a reliable tool for evaluating transporter-mediated drug-drug interactions. Recently, genetically modified cells (referred to as upcyte hepatocytes) have emerged as an expandable, noncancerous source of human hepatic cells. Herein, we quantified mRNA and protein levels of key hepatobiliary transporters and we assessed associated uptake activity in short- and long-term cultures of upcyte human hepatocytes (UHH) in comparison to cryopreserved primary human hepatocytes (cPHH).

Upcyte Human Hepatocytes: a Potent In Vitro Tool for the Prediction of Hepatic Clearance of Metabolically Stable Compounds.

In vitro models based on primary human hepatocytes (PHH) have been advanced for clearance (CL) prediction of metabolically stable compounds, representing state-of-the-art assay systems for drug discovery and development. Yet, limited cell availability and large interindividual variability of metabolic profiles remain shortcomings of PHH. Upcyte human hepatocytes (UHH) represent a novel hepatic cell system derived from PHH, exhibiting proliferative capacity for approximately 35 population doublings.

Two quantitative approaches for estimating content validity.

Instrument content validity is often established through qualitative expert reviews, yet quantitative analysis of reviewer agreements is also advocated in the literature. Two quantitative approaches to content validity estimations were compared and contrasted using a newly developed instrument called the Osteoporosis Risk Assessment Tool (ORAT). Data obtained from a panel of eight expert judges were analyzed.

The osteoporosis risk assessment tool: establishing content validity through a panel of experts.

Twenty-three items were initially developed for the Atkins Osteoporosis Risk Assessment Tool (ORAT) after a thorough examination of the literature. These items were reviewed for relevance to the domain of content by a panel of eight experts using Lynn's (1986) two-stage process for content validation. The Content Validity Index and the kappa coefficient of agreement were analyzed from panelists' quantitative ratings and 15 items were retained.