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mRNA expression levels of cytochrome P450 CYP1A2 , CYP3A4 , and CYP3A5 in the epidermis: a focus on individual differences among Japanese individuals
Xenobiotica. 2024 Apr 24:1-7. doi: 10.1080/00498254.2024.2344664. Online ahead of print.ABSTRACTVarious cytochrome P450 enzymes (CYPs) that contribute to drug metabolism are expressed in the skin. However, variation among individuals in CYP expression profiles is not well-understood.To investigate CYPs related to the metabolism of transdermal preparations in Japan, multiple skin tissue specimens of individuals of Japanese descent were prepared, and the mRNA expression levels of CYP1A2, CYP3A4, and CYP3A5 were measured. Associations between the expression patterns of these CYPs and body mass index (BMI) were also investigat...
Source: Xenobiotica - April 22, 2024 Category: Research Authors: Hiroko Makihara Mika Maezawa Kazusa Kaiga Toshihiko Satake Mayu Muto Yui Tsunoda Tsutomu Shimada Tomoko Akase Source Type: research

Monomethyl Auristatin E (MMAE), a Payload for Multiple Antibody Drug Conjugates (ADCs), Demonstrates Differential Red Blood Cell Partitioning Across Human and Animal Species
In this study, we have explored whether MMAE displays differential red blood cell (RBC) partitioning across species that may contribute to the different MMAE levels seen between human and animals.Experiments: To determine MMAE RBC partitioning, tritium labeled MMAE ([3H]-MMAE) was incubated in whole blood from mice, rats, monkeys and humans in vitro, then RBC partitioning was determined and compared across species. To test whether MMAE released from the ADC would show any difference in RBC partitioning, pinatuzumab vedotin or polatuzumab vedotin was administered to mice, rats, and monkeys. MMAE levels were measured in both...
Source: Xenobiotica - April 22, 2024 Category: Research Authors: Victor Yip Ola M Saad Doug Leipold Chunze Li Amrita Kamath Ben-Quan Shen Source Type: research

mRNA Expression Levels of Cytochrome P450 CYP1A2, CYP3A4, and CYP3A5 in the Epidermis: A Focus on Individual Differences Among Japanese Individuals
Xenobiotica. 2024 Apr 22:1-28. doi: 10.1080/00498254.2024.2344664. Online ahead of print.ABSTRACTVarious cytochrome P450 enzymes (CYPs) that contribute to drug metabolism are expressed in the skin. However, variation among individuals in CYP expression profiles is not well-understood.To investigate CYPs related to the metabolism of transdermal preparations in Japan, multiple skin tissue specimens of individuals of Japanese descent were prepared, and the mRNA expression levels of CYP1A2, CYP3A4, and CYP3A5 were measured. Associations between the expression patterns of these CYPs and body mass index (BMI) were also investiga...
Source: Xenobiotica - April 22, 2024 Category: Research Authors: Hiroko Makihara Mika Maezawa Kazusa Kaiga Toshihiko Satake Mayu Muto Yui Tsunoda Tsutomu Shimada Tomoko Akase Source Type: research

Preparation, characterisation, pharmacokinetics and distribution of esculin microspheres administered via intravitreal injection into rabbit brain
This study explored the distribution of esculin microspheres in rabbit brain tissue following intravitreal injection and investigated the possibility of direct entry of the drug into the brain through the eye, to develop a formulation with enhanced therapeutic efficacy against Parkinson's disease.Chitosan microspheres of esculin were prepared via an emulsification cross-linking method and their characteristics were evaluated, including angle of repose, bulk density, and swelling ratio. Furthermore, the pharmacokinetic parameters and brain tissue distribution in rabbits were compared among groups administered esculin eye dr...
Source: Xenobiotica - April 19, 2024 Category: Research Authors: Danqing Wu Rui Luo Yangnan Chen Zhiyun Zheng Shuangying Gui Ning He Source Type: research

Selection of a Suitable Animal Model to Evaluate Secretion of Drugs in the Human Milk: A Systematic Approach
Xenobiotica. 2024 Apr 18:1-23. doi: 10.1080/00498254.2024.2345283. Online ahead of print.ABSTRACTLack of data on drug secretion in human milk is a concern for safe use of drugs during postpartum.Clinical studies are often difficult to perform; despite substantial improvements in computational methodologies such as physiologically based pharmacokinetic modelling, there is limited clinical data to validate such models for many drugs.Various factors that are likely to impact milk to plasma ratio were identified. A literature search was performed to gather available data on milk composition, total volume of milk produced per d...
Source: Xenobiotica - April 18, 2024 Category: Research Authors: Riya Nilkant Chintha Kathiresan Namrata Kumar Steve Caritis Imam H Shaik Raman Venkataramanan Source Type: research

Developmental stage and infection status may affect drug distribution in the prostate of rats
Xenobiotica. 2024 Apr 18:1-13. doi: 10.1080/00498254.2024.2343892. Online ahead of print.ABSTRACTProstate inflammation is often treated with drugs which are ineffective. Antibacterial agents fail to reach the prostate epithelium, and the blood-prostate barrier (BPB) may affect the drug transport process. Factors affecting drug efficacy remain unclear.Rats were categorized into groups A and B, corresponding to adulthood and puberty, respectively. Group C included the model of chronic prostate infection. Dialysates of levofloxacin and cefradine were collected from the prostate gland and jugular vein and evaluated. Pharmacoki...
Source: Xenobiotica - April 18, 2024 Category: Research Authors: Ziyang Xu Lianzhan Sun Chang Yin Handa Wang Xue Wang Yunyun Yang Zhuo Wang Source Type: research

Exploring precision-cut liver slices for comparative xenobiotic metabolism profiling in swine and cattle
Xenobiotica. 2024 Apr 16:1-14. doi: 10.1080/00498254.2024.2343905. Online ahead of print.ABSTRACTIn vitro systems are useful tools for unravelling species differences in xenobiotic metabolism.The current work aimed to validate the technique of precision-cut liver slices (PCLS) for comparative studies on xenobiotic metabolism in swine and cattle.PCLS from swine (n = 3) and cattle (n = 3) were produced using a Brendel-VitronTM Tissue Slicer and cultured for 6 h. Tissue viability was preserved throughout the whole culture period.Metabolic viability was evaluated using the anthelmintics albendazole (ABZ) and fenbendazole (FBZ)...
Source: Xenobiotica - April 16, 2024 Category: Research Authors: Paula Ichinose Mar ía Victoria Miró Paula Viviani Juan Manuel Herrera Adri án Lifschitz Guillermo Virkel Source Type: research

Academic foreign compound metabolism - 'Quo vadis'?
Xenobiotica. 2024 Apr 12:1-5. doi: 10.1080/00498254.2024.2340740. Online ahead of print.NO ABSTRACTPMID:38606913 | DOI:10.1080/00498254.2024.2340740 (Source: Xenobiotica)
Source: Xenobiotica - April 12, 2024 Category: Research Authors: S C Mitchell R H Waring Source Type: research

Bioanalytical Approaches to Support the Development of Antibody-Oligonucleotide Conjugate (AOC) Therapeutic Proteins
Xenobiotica. 2024 Apr 12:1-23. doi: 10.1080/00498254.2024.2339983. Online ahead of print.ABSTRACTRNA interference (RNAi) is a biological process that evolved to protect eukaryotic organisms from foreign genes delivered by viruses. This process has been adapted as a powerful tool to treat numerous diseases through the delivery of small-interfering RNAs (siRNAs) to target cells to alter aberrant gene expression.Antibody-oligonucleotide conjugates (AOCs) are monoclonal antibodies with complexed siRNA or antisense oligonucleotides (ASOs) that have emerged to address some of the challenges faced by naked or chemically conjugate...
Source: Xenobiotica - April 12, 2024 Category: Research Authors: Anthony Murphy Ryan Hill Michael Berna Source Type: research