A retrospective analysis of non-specific binding in in vitro metabolism assays: Impact of protein and drug concentration on microsomal free fraction

DMDG Open 2024 -- Non-specific binding of drugs to microsomes can profoundly influence the outcome of in vitro metabolism assays and represents a key consideration in the calculation of kinetic parameters associated with drug-drug interaction (DDI) investigations or in vitro-in vivo extrapolations based on scaling of intrinsic clearance data. Recent regulatory guidance documents advocate the determination of the microsomal free fraction (fumic) and recommend that protein concentrations “are usually less than 1 mg/mL” (FDA, 2020) or “should be minimised” (ICH, 2024). Labcorp cytochrome P450 inhibition investigations include the determination of the fumic parameter in our standard study design. In this retrospective review, we have collated data from 39 recent studies to identify the proportion of compounds which show significant binding at typical incubation concentrations and the protein and concentration dependency of this binding. These data can provide a better understanding of assay conditions where binding has a high impact and facilitates the potential streamlining of processes with regard to experimental complexity and timelines.

Evaluation and comparison of HµREL® and HEPATOPAC® hepatic co-culture test systems for the prediction of metabolic clearance and metabolite profiling

DMDG Open 2024 -- Understanding the metabolic clearance and metabolism of xenobiotics across species is important for ensuring appropriate toxicological data is obtained, and for the successful prediction of human pharmacokinetics. Obtaining reliable in vitro metabolic clearance data and assessing the metabolite profiles of metabolically stable compounds using traditional hepatocytes suspensions has been challenging due to limited enzyme stability. Several test systems now offer extended enzyme stability and incubation times to more accurately assess the metabolic stability of metabolic stable compounds. Here the HμREL® co‑cultured hepatic model, which offers primary cryopreserved hepatocytes cultured together with cells of a non-parenchymal, stromal type and the HEPATOPAC® co-cultured hepatic model, which form hepatocyte islands surrounded by supportive stromal cells, were assessed and compared.

Labcorp to Acquire Select Outreach Services From Ballad Health

Johnson City, Tenn. and BURLINGTON, N.C. , Sept. 9, 2024 --  Ballad Health announced today it has reached agreement on a strategic collaboration with Labcorp, a global leader of innovative and comprehensive laboratory services, to provide outreach laboratory services across the Appalachian Highlands region.

Labcorp to Speak at the Baird 2024 Global Healthcare Conference

BURLINGTON, N.C. , Sept. 3, 2024 /PRNewswire/ --  Labcorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, announced today that members of the executive management team will participate in a presentation at the Baird 2024 Global Healthcare Conference on Tuesday,

Infirmary Health laboratory management transition increases savings, gains efficiencies and improves service

In 2020, Infirmary Health transitioned laboratory management to Labcorp from another commercial lab service provider. Infirmary Health selected Labcorp among other laboratories to provide additional data and analytics as well as increased cost savings. 

Cardiac single-cell degeneration in common marmosets (Callithrix jacchus)

ESVP/ESTP/ECVP Congress 2024 -- In the last two decades, common marmosets (Callithrix jacchus) have been more frequently used in preclinical toxicity studies due to their physiological similarities with humans. For instance, several surface receptors on marmoset lymphocytes are cross-reactive with monoclonal antibodies against the corresponding human variant and the hepatic metabolism mimics the human pathways more closely than other nonhuman primates (NHPs) (Han et al., 2022). Nevertheless, marmosets differ from macaques regarding spontaneous diseases and background pathology and only few descriptions are available in the literature that might complicate the interpretation of findings in this species. Thus far, myocardial degeneration has been described by Okazaki et al. as spontaneous background pathology in minimal to slight magnitude in single animals (5/59). Necrosis in the heart is described very rarely in the literature (2/597 animals in David et al., 2009).

Mysterious lesion in the brain of a cynomolgus monkey (Macaca fascicularis): What’s your diagnosis?

ESVP/ESTP/ECVP Congress 2024 -- In recent years, the development of new drug modalities has underlined the importance of nonhuman primates in biomedical research. Simultaneously, the central nervous system (CNS) has gained importance as a target for different drug modalities including gene therapeutics (Gao et al., 2024). Therewith, the CNS is often closely examined and a popular subject of lively discussions on the cause and significance of unusual findings. Herewith, the authors describe an exceptional finding in the brain of a cynomolgus monkey (Macaca fascicularis) of unknown etiology.