Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results.
Summary of "Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results."
The field of toxicology is currently undergoing a global paradigm shift to use of in vitro approaches for assessing the risks of chemicals and drugs in a more mechanistic and high throughput manner than current approaches relying primarily on in vivo testing. However, reliance on in vitro data entails a number of new challenges associated with translating the in vitro results to corresponding in vivo exposures. Physiologically based pharmacokinetic (PBPK) modeling provides an effective framework for conducting quantitative in vitro to in vivo extrapolation (QIVIVE). Their physiological structure facilitates the incorporation of in silico- and in vitro-derived chemical-specific parameters in order to predict in vivo absorption, distribution, metabolism and excretion. In particular, the combination of in silico- and in vitro parameter estimation with PBPK modeling can be used to predict the in vivo exposure conditions that would produce chemical concentrations in the target tissue equivalent to the concentrations at which effects were observed with in vitro assays of tissue/organ toxicity. This review describes the various elements of QIVIVE and highlights key aspects of the process, with an emphasis on extrapolation of in vitro metabolism data to predict in vivo clearance as the key element. Other important elements include characterization of free concentration in the toxicity assay and potential complications associated with intestinal absorption and renal clearance. Examples of successful QIVIVE approaches are described ranging from a simple steady-state approach that is suitable for a high throughput environment to more complicated approaches requiring full PBPK models.
Affiliation
Center for Human Health Assessment, The Hamner Institutes for Health Sciences , Research Triangle Park, Durham, NC , USA.
Journal Details
This article was published in the following journal.
Name: Critical reviews in toxicology
ISSN: 1547-6898
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22667820
- DOI: http://dx.doi.org/10.3109/10408444.2012.692115
Medical and Biotech [MESH] Definitions
Ristocetin
An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro.
Biological Assay
A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc.
Embryo Transfer
The transfer of mammalian embryos from an in vivo or in vitro environment to a suitable host to improve pregnancy or gestational outcome in human or animal. In human fertility treatment programs, preimplantation embryos ranging from the 4-cell stage to the blastocyst stage are transferred to the uterine cavity between 3-5 days after FERTILIZATION IN VITRO.
Cell Fusion
Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization.
Tumor Stem Cell Assay
A cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents.
PubMed Articles
Introduction: Reliable in vitro and in silico assays as alternatives for in vivo developmental toxicity studies are urgently needed, for the replacement, reduction and refinement (3Rs) of animal use...
The present study determines the relative developmental toxicity potencies of retinoids in the embryonic stem (ES)-D3 cell differentiation assay of the embryonic stem cell test, and compares the outco...
The purpose of this study was to evaluate the in vitro and in vivo antitumor efficacy and the dose dependent toxicity of camptothecin nanosuspension (Nano-CPT) comparing with that of topotecan (TPT)....
There is an urgent need for in vitro screening assays to evaluate nanoparticle (NP) toxicity. However, the relevance of in vitro assays is still disputable. We administered doses of TiO(2) NPs of diff...
Abstract Engineered nanoparticles (NPs) are widely used in different technologies but their unique properties might also cause adverse health effects. In reviewing recent in vitro and in vivo genotoxi...
Clinical Trials
A Real Life Evaluation of the Performance of a Large Volume Nebulizer
Continuous albuterol has become the standard of care for patients in status asthmaticus. We have previously performed an in-vitro study comparing 4 different brands of continuous nebulizer...
Intrauterine Embryo Development With ANECOVA Device
We aim to compare the morphological and chromosomal features of human embryos cultured In Vitro versus those developed in a new In Vivo culture system with encapsulation in utero as well a...
Use of the MiCK Assay for Apoptosis in AML
A previous preliminary study performed at Vanderbilt University with funding from the Leukemia Society of America demonstrated that the response of leukemia cells in vitro to the chemother...
B-cryptoxanthin and Phytosterols on Bone Remodeling and Cardiovascular Risk Factors
We, the investigators, aim to study, in vitro and in vivo, the bioavailability of added b-cryptoxanthin and phytosterols and evaluate in vivo its effect on biochemical markers of bone remo...
T-Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Hematologic Malignancies
Objectives: 1. To evaluate disease free survival after Campath 1H-based in vivo T-cell depletion and non-myelo-ablative ablative stem cell transplantation in patients with hemato...
