Xenobiotica最新文献

Bioavailability and dose proportionality of a highly lipophilic phenolic antioxidant.

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-02-18 DOI: 10.1080/00498254.2025.2465237

Elena A Yanovskaya, Galina A Frelikh, Alexander P Lakeev, Vera I Smolyakova, Galina A Chernysheva

{"title":"Bioavailability and dose proportionality of a highly lipophilic phenolic antioxidant.","authors":"Elena A Yanovskaya, Galina A Frelikh, Alexander P Lakeev, Vera I Smolyakova, Galina A Chernysheva","doi":"10.1080/00498254.2025.2465237","DOIUrl":"https://doi.org/10.1080/00498254.2025.2465237","url":null,"abstract":"IBP (2,6-diisobornyl-4-methylphenol) is a camphene derivative with unique pharmacological properties and low toxicity. It exhibits pronounced antioxidant and membrane-protective effects, making it a promising cardio- and neuroprotector.The aim of the study was investigating the pharmacokinetics of IBP in rats after intravenous (1 mg/kg) and oral administration at three doses (10, 25, 50 mg/kg). Specifically, we focused on assessing the bioavailability and dose proportionality following oral administration.Blood samples were collected via a jugular vein catheter, and plasma samples were analyzed using a validated HPLC-MS/MS method. The calculation of pharmacokinetic parameters was performed by both non-compartmental and compartmental approaches. The proposed dosage form for intravenous administration was a multicomponent mixture containing N-methyl-2-pyrrolidone.Concentration of IBP in the body after intravenous administration decreased over time, exhibiting bi-exponential decay kinetics. IBP reached peak concentrations immediately and was rapidly distributed into the peripheral compartment after intravenous administration. The systemic exposure after oral administration was proportional to the dose. The calculated absolute oral bioavailability of IBP was no more than 20%.The value of the average half-life of IBP after intravenous administration exceeded similar values after oral administration by 1.5-1.6 times.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-33"},"PeriodicalIF":1.3,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nrf2 Signaling Pathway Studies in Drosophila melanogaster: Parallel Roles in Human Health and Insect Environmental Responses.

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-02-11 DOI: 10.1080/00498254.2025.2465239

Jingyi Li, Shushen Sun, Ying Li, Mengzhe Tian, Xinyi Li, Suxia Ren, Zengyi Huang, Yiwen Wang, Shaoshan Du

{"title":"Nrf2 Signaling Pathway Studies in Drosophila melanogaster: Parallel Roles in Human Health and Insect Environmental Responses.","authors":"Jingyi Li, Shushen Sun, Ying Li, Mengzhe Tian, Xinyi Li, Suxia Ren, Zengyi Huang, Yiwen Wang, Shaoshan Du","doi":"10.1080/00498254.2025.2465239","DOIUrl":"https://doi.org/10.1080/00498254.2025.2465239","url":null,"abstract":"The Nrf2 signaling pathway is crucial for cellular defense against oxidative stress and xenobiotic toxicity, highlighting its importance in both human health and environmental responses.This review focuses on the dual role of Drosophila melanogaster in Nrf2 research: we utilized the PubMed database to collect and summarized research articles on fruit fly Nrf2 studies published in the past decade, using keywords such as \"Nrf2,\" \"CncC,\" and \"Drosophila.\"We found that Drosophila melanogaster, as a classical model organism for studying human diseases such as neurodegenerative disorders, cancers, and diabetes, and as an insect model for investigating xenobiotic responses and pesticide resistance, is particularly well-suited for exploring the diverse and complex functions of Nrf2 pathway.Additionally, Natural products such as curcumin and quercetin can modulate Nrf2 activity for cytoprotection. Utilizing D. melanogaster's genetic tools and short life cycle, researchers can discover new therapeutics and study their mechanisms.This twofold exploration not only advances our understanding of Nrf2 in human health but also provides insights into pest control strategies through enhanced insect resistance mechanisms. Continued research in this area is essential for developing innovative treatments and effective pest management approaches.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-30"},"PeriodicalIF":1.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimising pirfenidone dosage regimens in idiopathic pulmonary fibrosis: towards a guide for personalised treatment.

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-01-26 DOI: 10.1080/00498254.2025.2450440

Nastia Tsyplakova, Georgios Ismailos, Vangelis D Karalis

{"title":"Optimising pirfenidone dosage regimens in idiopathic pulmonary fibrosis: towards a guide for personalised treatment.","authors":"Nastia Tsyplakova, Georgios Ismailos, Vangelis D Karalis","doi":"10.1080/00498254.2025.2450440","DOIUrl":"https://doi.org/10.1080/00498254.2025.2450440","url":null,"abstract":"Idiopathic Pulmonary Fibrosis (IPF) is a chronic respiratory disorder for which pirfenidone is the recommended first-line anti-fibrotic treatment. While pirfenidone has demonstrated efficacy in slowing the progression of IPF, its use is associated with several challenges and unresolved issues that impact patient outcomes. Pirfenidone administration can result in gastrointestinal side effects, photosensitivity reactions, and significant drug interactions, particularly in patients with hepatic impairment. For those who experience intolerable side effects, dose reductions or temporary discontinuations are frequently employed. However, there is limited data on the efficacy of reduced doses, creating uncertainty about the balance between tolerability and therapeutic benefit.The aim of this study is to evaluate the currently proposed dosage adjustments and to develop new dosage regimens tailored to the needs of patients. Simulations were conducted to explore pirfenidone pharmacokinetics under various challenging conditions, including dose titration, withdrawal, retitration, moderate and severe hepatic impairment, co-administration of moderate (e.g. omeprazole) and strong (e.g. smoking) inducers of the CYP1A2 enzyme, gastrointestinal adverse events, and photosensitivity reactions.Simulations led to specific recommendations for physicians regarding dosage regimens in each condition. The recommended dosage adjustments are designed to maintain concentrations within acceptable levels, ensuring both safe and effective treatment.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-12"},"PeriodicalIF":1.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inorganic mercury pharmacokinetics in man: a hybrid model. 无机汞在人体内的药代动力学：一个混合模型。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-01-22 DOI: 10.1080/00498254.2024.2448979

Fred Farris, Ayda Awaness, Joe Su

{"title":"Inorganic mercury pharmacokinetics in man: a hybrid model.","authors":"Fred Farris, Ayda Awaness, Joe Su","doi":"10.1080/00498254.2024.2448979","DOIUrl":"10.1080/00498254.2024.2448979","url":null,"abstract":"A four-compartment model is presented that simulates inorganic mercury [Hg(II)] pharmacokinetics in blood, tissue, and excreta over a 70-day period. Simulations are validated against data collected from five human subjects, and previously analyzed.In the model, two compartments simulate Hg(II) in blood: one for mobile-Hg(II) and the other for immobile-Hg(II). Two corresponding compartments simulate Hg(II) in tissue. Mobile-Hg(II) represents Hg(II) available for transport across cell membranes. Immobile-Hg(II) represents Hg(II) that is not easily transported.Following dosing, blood total-Hg(II) droped rapidly in all subjects. Blood mobile-Hg(II) also droped rapidly with a concomitant rise in blood immobile-Hg(II). For four subjects, immobile-Hg(II) became the dominant Hg(II) species in blood by day 4. For subject five, mobile-Hg(II) remained dominant in blood for the study duration.Tissue mobile-Hg(II) declined rapidly for four of the subjects, with a simultaneous rapid rise in tissue immobile-Hg(II). In subject 5, tissue mobile-Hg(II) declined linearly, and immobile-Hg(II) accumulated slowly in tissue. For all subjects, tissue mobile-Hg(II) is the primary source of fecal Hg(II). The major source for Hg(II) excreted into the urine is immobile-Hg(II) from tissue.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-12"},"PeriodicalIF":1.3,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dolutegravir metabolism: impact of genetic variations on uridine diphosphate glucuronosyltransferase subfamilies. 多替格拉韦代谢：遗传变异对尿苷二磷酸葡萄糖醛酸转移酶亚家族的影响。

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-01-20 DOI: 10.1080/00498254.2025.2453983

Kouji Tagawa, Yoshihiro Maruo

{"title":"Dolutegravir metabolism: impact of genetic variations on uridine diphosphate glucuronosyltransferase subfamilies.","authors":"Kouji Tagawa, Yoshihiro Maruo","doi":"10.1080/00498254.2025.2453983","DOIUrl":"https://doi.org/10.1080/00498254.2025.2453983","url":null,"abstract":"Dolutegravir (DTG) is a key drug used to treat human immunodeficiency virus type-1 (HIV-1) infections. Adverse events (AEs) of DTG treatment, including headache, anxiety, depression, insomnia, and abnormal dreams, are influenced by sex, body weight, age, and serum bilirubin levels. DTG is mainly metabolised by members of the uridine diphosphate glucuronosyltransferase 1A subfamilies (UGT1As), especially UGT1A1.Some studies suggest a relationship between UGT1A1 variants and AEs. The aim of this study was to identify UGT1A isoforms that exhibit DTG glucuronidation activity and determine the relationship between UGT1A variants and DTG glucuronidation in vitro.UGT1A1, UGT1A3, UGT1A9, and UGT1A10 exhibited DTG glucuronidation activity, of which UGT1A1 was the most active. Furthermore, variants of these isoforms showed decreased DTG glucuronidation activity. The different variants of UGT1As, such as UGT1A1.6, UGT1A1.7, UGT1A1.35, UGT1A1.63, UGT1A3.5, UGT1A9.2, UGT1A10M59I, and UGT1A10T202I, showed reduced glucuronidation activity towards DTG in comparison with the wild-type UGT1As.This study elucidates the relationship between UGT1A variants and the levels of glucuronidation associated with each variant.Checking for UGT1As may be helpful in predicting potential toxicities and adverse effects related to DTG treatment.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-8"},"PeriodicalIF":1.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The impact of CYP3A5, NR1I2, and POR polymorphisms on tacrolimus dose-adjusted concentration and clinical outcomes in adult allogeneic haematopoietic stem cell transplantation. CYP3A5、NR1I2和POR多态性对成人异基因造血干细胞移植中他克莫司剂量调整浓度和临床结果的影响

IF 1.3 4区医学

Xenobiotica Pub Date : 2025-01-07 DOI: 10.1080/00498254.2024.2448967

Yuan Gao, Jingjing Ma

{"title":"The impact of CYP3A5, NR1I2, and POR polymorphisms on tacrolimus dose-adjusted concentration and clinical outcomes in adult allogeneic haematopoietic stem cell transplantation.","authors":"Yuan Gao, Jingjing Ma","doi":"10.1080/00498254.2024.2448967","DOIUrl":"10.1080/00498254.2024.2448967","url":null,"abstract":"Polymorphisms in genes related to drug-metabolising enzymes may affect tacrolimus exposure. This study aimed to assess the influence of CYP3A5, NR1I2, and POR polymorphisms on tacrolimus pharmacokinetics and outcomes in allogeneic haematopoietic stem cell transplantation (HSCT).Forty-six adult patients receiving oral tacrolimus at an initial dose of 0.03 mg/kg/day for acute graft versus host disease (GVHD) prophylaxis after allogeneic HSCT were enrolled in this retrospective study. Genetic polymorphisms were detected in relation to concentration/dose (C/D) ratios of tacrolimus and the incidence of acute GVHD and acute kidney injury (AKI).The CYP3A5 *3/*3 genotype and co-administration of voriconazole were significantly associated with increased C/D ratios of tacrolimus (p < 0.05). NR1I2 8055CC presents a significantly higher tacrolimus C/D ratio compared with carriers of 8055CT and 8055TT genotypes in allogeneic HSCT recipients with the CYP3A5*1 allele (p = 0.033). Younger age and recipients with the CYP3A5*1 allele were significantly associated with higher incidence of II-IV acute GVHD post-transplantation.CYP3A5*3, NR1I2 8055C > T, and concomitant use of voriconazole are important determinants affecting tacrolimus pharmacokinetics. Moreover, CYP3A5*1 allele and younger age are independent risk factors for II-IV acute GVHD in HSCT recipients.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of CYP3A5 polymorphism and renal impairment on the drug interaction between venetoclax and fluconazole in acute myeloid leukaemia patients. CYP3A5多态性与肾损害对急性髓系白血病患者维妥乐与氟康唑药物相互作用的影响。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-12-20 DOI: 10.1080/00498254.2024.2442431

Takahiro Kobayashi, Honami Sato, Yumiko Akamine, Yayoi Fukushi, Naoto Takahashi, Masatomo Miura

{"title":"Effects of CYP3A5 polymorphism and renal impairment on the drug interaction between venetoclax and fluconazole in acute myeloid leukaemia patients.","authors":"Takahiro Kobayashi, Honami Sato, Yumiko Akamine, Yayoi Fukushi, Naoto Takahashi, Masatomo Miura","doi":"10.1080/00498254.2024.2442431","DOIUrl":"10.1080/00498254.2024.2442431","url":null,"abstract":"The aim of this study was to investigate the effects of renal function and CYP3A5 polymorphism on the drug interaction between venetoclax and fluconazole in thirty acute myeloid leukaemia patients.The area under the plasma concentration-time curve (AUC) and trough concentration (C0) of venetoclax and the fluconazole C0 were obtained from plasma samples on day 7 later after initiation of venetoclax 200 mg/day combined with fluconazole.The fluconazole C0 values in patients with moderate and severe renal impairment were significantly higher than those in patients with normal or mild impairment (median values 7037, 6234, and 4813 ng/mL, respectively, P = 0.026).In patients with CYP3A5*3/*3 genotype, the AUC0-24 and C0 of venetoclax were not associated with fluconazole C0; however, in patients with a CYP3A5*1 allele, a significant positive correlation was observed between venetoclax C0 and fluconazole C0 (r = 0.782, P = 0.004).The metabolism of venetoclax by CYP3A4 is inhibited even at low fluconazole C0. In patients with a CYP3A5*1 allele, CYP3A5 is inhibited when high fluconazole C0 is induced by renal impairment.The dose of fluconazole for prophylaxis may be 100 mg in patients with severe renal impairment receiving venetoclax therapy.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-6"},"PeriodicalIF":1.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Noise - an insidious stressor affecting xenobiotic metabolism? 噪音——影响异种生物代谢的潜在压力源？

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-12-18 DOI: 10.1080/00498254.2024.2441675

Rosemary Waring, Stephen Mitchell

引用次数: 0

Preclinical assessment of the PI3Kα selective inhibitor inavolisib and prediction of its pharmacokinetics and efficacious dose in human. PI3Kα 选择性抑制剂 Inavolisib 的临床前评估及其在人体中的药代动力学和有效剂量预测

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-10-01 Epub Date: 2024-12-04 DOI: 10.1080/00498254.2024.2415103

Laurent Salphati, Jodie Pang, Emile G Plise, Jonathan Cheong, Marie-Gabrielle Braun, Lori S Friedman, Rebecca Hong Thibodeau, Allan Jaochico, Ryan Johnson, Ning Liu, Michelle Nannini, Deepak Sampath, Kyung Song, Emily J Hannan, Steven T Staben

{"title":"Preclinical assessment of the PI3Kα selective inhibitor inavolisib and prediction of its pharmacokinetics and efficacious dose in human.","authors":"Laurent Salphati, Jodie Pang, Emile G Plise, Jonathan Cheong, Marie-Gabrielle Braun, Lori S Friedman, Rebecca Hong Thibodeau, Allan Jaochico, Ryan Johnson, Ning Liu, Michelle Nannini, Deepak Sampath, Kyung Song, Emily J Hannan, Steven T Staben","doi":"10.1080/00498254.2024.2415103","DOIUrl":"10.1080/00498254.2024.2415103","url":null,"abstract":"1. Small molecule inhibitors of the PI3K pathway have been extensively investigated as potential anticancer agents. Among the effectors in this pathway, PI3Kα is the kinase most frequently associated with the development of tumours, through mutations and amplifications of the PIK3CA gene encoding the p110α catalytic subunit.2. Inavolisib (GDC-0077) is a potent and PI3Kα-selective inhibitor that also specifically triggers the degradation of the mutant p110α protein.3. We characterised inavolisib ADME properties in preclinical in vitro and in vivo studies, assessed its efficacy in the PIK3CA mutant KPL-4 breast cancer xenograft model, and predicted its pharmacokinetics and efficacious dose in humans.4. Inavolisib had a moderate permeability (1.9•10-6 cm/s) in MDCK cells and was a P-gp and Bcrp1 substrate. It appeared metabolically stable in hepatocytes incubations from human and preclinical species. The systemic clearance was low in mouse, monkey and dog and high in rat. Oral bioavailability ranged from 57.5% to 100%. Inavolisib was efficacious in the KPL-4 sub-cutaneous xenograft model.5. The PK/PD model parameters estimated from the efficacy study, combined with PBPK model-predicted human PK profiles, projected that a dose of 3 mg could lead to clinical response. Inavolisib is currently being tested in phase 3 trials.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"808-820"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vaginal administration of 17-alpha hydroxyprogesterone caproate appears to be safe in non-pregnant female rats and rabbits. 经阴道给药癸酸 17-α 羟孕酮似乎对未怀孕的雌性大鼠和兔子是安全的。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-10-01 Epub Date: 2024-11-25 DOI: 10.1080/00498254.2024.2432900

Imam H Shaik, Nupur Chaphekar, Vignesh Vasudevan, Ali Alshabi, Athbah AlOwaifeer, Wenchen Zhao, Steve Caritis, Raman Venkataramanan

{"title":"Vaginal administration of 17-alpha hydroxyprogesterone caproate appears to be safe in non-pregnant female rats and rabbits.","authors":"Imam H Shaik, Nupur Chaphekar, Vignesh Vasudevan, Ali Alshabi, Athbah AlOwaifeer, Wenchen Zhao, Steve Caritis, Raman Venkataramanan","doi":"10.1080/00498254.2024.2432900","DOIUrl":"10.1080/00498254.2024.2432900","url":null,"abstract":"Intramuscular (250 mg once weekly) or subcutaneous (275 mg once weekly) injections of 17-hydroxyprogesterone caproate (17-OHPC) has been utilised to prevent recurent spontaneous preterm birth in pregnant women with a short cervix or those with a prior preterm birth but its efficacy in these conditions has been questioned. It is unclear whether adequate concentrations of 17-OHPC reach the suspected target organs such as the cervix and uterus following either IM or SC administration.The objective of this study was to determine feasibility and safety of vaginal administration of 17-OHPC in adult female Sprague Dawley rats and female New Zealand rabbits.Gels containing 17-OHPC were administered intravaginally to rats and rabbits for 10 consecutive days. After the last dose, serial blood samples and terminal uterine and adipose tissue samples were collected. 17-OHPC concentrations were measured by LC-MS-MS.Tissue histology showed that intravaginal administration of 17-OHPC was safe. There was no renal or hepatic toxicity as measured by liver function and kidney function tests.Intravaginal administration of 17-OHPC resulted in low systemic plasma concentrations but substantially higher uterus and adipose tissue concentrations of 17-OHPC. Composition of the formulation affected the tissue distribution of 17-OHPC.Future studies warrant further evaluation of the effect and safety of daily intravaginal administration of 17-OHPC gel in pregnant animals.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"821-830"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0