IF 1.3 4区医学

Xenobiotica Pub Date : 2024-11-18 DOI: 10.1080/00498254.2024.2427032

Katarina Danković, Nikola Stefanović, Tatjana Cvetković, Stevan Vujić, Maša Jović, Branka Mitić, Radmila Veličković-Radovanović

{"title":"Potential influence of interleukin-6 -174G/C gene polymorphism on kidney graft function and tacrolimus dose requirements: five-year follow-up.","authors":"Katarina Danković, Nikola Stefanović, Tatjana Cvetković, Stevan Vujić, Maša Jović, Branka Mitić, Radmila Veličković-Radovanović","doi":"10.1080/00498254.2024.2427032","DOIUrl":"10.1080/00498254.2024.2427032","url":null,"abstract":"1. introduction: The study aimed to investigate the influence of interleukin (IL)-6 -174 G/C gene polymorphism on graft function (defined as estimated glomerular filtration rate, eGFR), as well as on the tacrolimus (Tac) pharmacokinetics during the five years after kidney transplantation.2. methods: The study included 115 Caucasian kidney transplant recipients on Tac-based immunosuppression. The patients were followed between 6 and 60 post-transplantation months. Interleukin-6 and CYP3A5 genotyping were performed.3. results: Patients carrying the IL-6 -174GG genotype had lower eGFR values compared to the patients with the IL-6 -174GC and -174CC genotypes at the 12th, 48th and 60th post-transplantation months. The linear regression analysis indicated that eGFR at the 6th post-transplantation month and IL-6 -174 G/C polymorphism are independent predictors of eGFR values in the late post-transplantation period. The IL-6 -174GG genotype carriers had lower dose-adjusted trough concentration (C0/D) of Tac compared to the IL-6 C allele carriers during the entire observation period (except at the 24th month), while this effect was independent of the CYP3A5 genotype within three years post-transplantation.4. conclusion: Interleukin-6 genotyping could be an additional tool to categorise patients towards the risk of graft deterioration in the long-term post-transplantation period. The IL-6 genotyping could be supportive in genotype-guided dosing of Tac.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629242","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

Preclinical metabolism and disposition of [¹⁴C]GFH009, a novel selective CDK9 inhibitor. 新型选择性 CDK9 抑制剂 [14C]GFH009 的临床前代谢和处置。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-11-15 DOI: 10.1080/00498254.2024.2428716

Li Wang, Jin-Zhu Zhao, Fu-Sheng Zhou, Jiong Lan, Qiang Lu, Hong-Can Ren

{"title":"Preclinical metabolism and disposition of [14C]GFH009, a novel selective CDK9 inhibitor.","authors":"Li Wang, Jin-Zhu Zhao, Fu-Sheng Zhou, Jiong Lan, Qiang Lu, Hong-Can Ren","doi":"10.1080/00498254.2024.2428716","DOIUrl":"https://doi.org/10.1080/00498254.2024.2428716","url":null,"abstract":"GFH009 is a potent and highly selective cyclin-dependent kinase 9 (CDK9) inhibitor currently under phase II clinical trials. In this study, we investigated the metabolism and disposition of GFH009 in Sprague-Dawley (SD) rats, as well as in vitro metabolism of CD-1 mouse, SD rat, beagle dog, cynomolgus monkey, and human.A radiolabelled study indicated that [14C]GFH009 was quickly and widely distributed throughout the body, but presented low levels in brain, testis, and epididymis after a single intravenous dose of 6 mg (100 µCi)/kg to SD rats.GFH009 undergoes systemic metabolic changes, primarily through O-demethylation, oxidation to carboxylic acid and N-dealkylation, cleavage off the methoxyisopropyl moiety being a minor pathway. These metabolic pathways were found to be mainly consistent both in vitro and in vivo.In SD rats, GFH009 was rapidly and completely eliminated, with faeces serving as the major excretion pathway and urine serving as the minor one. Besides, the major clearance pathway for GFH009 was excretion and the minor one was metabolism.GFH009 exhibits favourable drug metabolism and pharmacokinetics (DMPK) properties, which provides valuable insights into the disposition of GFH009 and can be used to guide future clinical studies.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-9"},"PeriodicalIF":1.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629243","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 benzophenone-3 on the liver and thyroid of adult zebrafish. 二苯甲酮-3 对成年斑马鱼肝脏和甲状腺的影响

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-11-13 DOI: 10.1080/00498254.2024.2429724

Felismário Medeiros da Silva, Renan Pena Modesto, Mirelly Cândida Cávoli Lira, Eduardo Libanio Reis Santos, Jeffesson de Oliveira-Lima

{"title":"Effects of benzophenone-3 on the liver and thyroid of adult zebrafish.","authors":"Felismário Medeiros da Silva, Renan Pena Modesto, Mirelly Cândida Cávoli Lira, Eduardo Libanio Reis Santos, Jeffesson de Oliveira-Lima","doi":"10.1080/00498254.2024.2429724","DOIUrl":"https://doi.org/10.1080/00498254.2024.2429724","url":null,"abstract":"1. Benzophenone-3 (BP-3), commonly known as oxybenzone, is an organic compound that acts as a sunscreen, protecting the skin from UVA and UVB rays. Thus, the objective of this study was to investigate the effects of BP-3 on the liver and thyroid using morphological and biochemical approaches.2. Adult male zebrafish were randomly assigned to three groups, each with three repetitions (n = 10 per group): water control, solvent control (0.01% ethanol), and 1 μg/L of BP-3, using a static exposure system for 96 hours. After the experiment, histopathological analyses of the liver and thyroid were performed, along with histochemical analyses (glycogen) and biochemical evaluations of the antioxidant enzymes Superoxide Dismutase (SOD) and Catalase (CAT).3. Exposure to BP-3 resulted in significant histopathological changes in the liver of Danio rerio, increasing the frequency of circulatory disturbances, progressive changes, inflammatory responses, and regressive changes. On the other hand, the thyroid gland did not show any morphological changes during exposure to BP-3, maintaining its typical structure with follicles. There was a significant increase in SOD activity, while CAT showed no changes after 96 hours of exposure.4. The results obtained demonstrate that exposure to BP-3 causes significant morphophysiological changes in the liver of D. rerio, highlighting not only the negative impacts on the health of these organisms but also the ecotoxicological potential of the substance and its consequences for aquatic biota in contaminated environments.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-11"},"PeriodicalIF":1.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629241","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

Notable drug-drug interaction between omeprazole and voriconazole in CYP2C19 *1 and *2 (rs4244285, 681G>A) alleles in vitro. 奥美拉唑和伏立康唑在体外 CYP2C19 *1 和 *2 (rs4244285, 681G>A)等位基因中发生显著的药物相互作用。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-10-28 DOI: 10.1080/00498254.2024.2421513

Xue Li

{"title":"Notable drug-drug interaction between omeprazole and voriconazole in CYP2C19 *1 and *2 (rs4244285, 681G>A) alleles in vitro.","authors":"Xue Li","doi":"10.1080/00498254.2024.2421513","DOIUrl":"https://doi.org/10.1080/00498254.2024.2421513","url":null,"abstract":"The drug-drug interaction (DDI) and CYP2C19 genetic variation can lead to a high blood concentration of voriconazole. CYP2C19 is a highly genetically polymorphic enzyme, and CYP2C19*2 is more frequent among Asians associated with reduced metabolism of drugs. Clinical study found that co-administration with omeprazole significantly increased voriconazole concentrations and there was an additive effect in CYP2C19*2 allele.CYP2C19 rs4244285 (681G>A) is the key polymorphism of CYP2C19*2 allele. This study aims to describe the in vitro effects of omeprazole on CYP2C19*1 and *2 (681G>A), and determine how CYP2C19 polymorphisms influence the DDI between omeprazole and voriconazole.Using the lentiviral expression system, we successfully generated HepG2-derived cell lines stably expressing CYP2C19*1 and *2 (681G>A). The results showed that the CYP2C19 mRNA level, protein level, and enzymatic activity were lower in HepG2-CYP2C19*2 (681G>A) than HepG2-CYP2C19*1 cells. Our study also showed that the inhibition rates of omeprazole on voriconazole had no significantly differences between CYP2C19*1 and *2 (681G>A). But the IC50 of omeprazole on CYP2C19*1 slightly lower than CYP2C19*2 (681G>A).Moreover, omeprazole inhibited CYP2C19 protein level in cells carrying CYP2C19*1 and CYP2C19*2 (681G>A). Our study demonstrated that omeprazole could inhibit voriconazole metabolism in both CYP2C19*1 and CYP2C19*2 (681G>A).","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-8"},"PeriodicalIF":1.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509243","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

Justification of widened dissolution specifications of an extended-release product using physiologically based biopharmaceutics modeling. 利用基于生理学的生物药剂学建模证明扩大缓释产品溶出度规格的合理性

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-10-14 DOI: 10.1080/00498254.2024.2411980

Adithya Karthik Bhattiprolu, Sivacharan Kollipara, Rajkumar Boddu, Tausif Ahmed

{"title":"Justification of widened dissolution specifications of an extended-release product using physiologically based biopharmaceutics modeling.","authors":"Adithya Karthik Bhattiprolu, Sivacharan Kollipara, Rajkumar Boddu, Tausif Ahmed","doi":"10.1080/00498254.2024.2411980","DOIUrl":"10.1080/00498254.2024.2411980","url":null,"abstract":"Drug products meeting the dissolution specifications is crucial in order to ensure consistent clinical performance. However, in certain cases, wider dissolution specifications may be required based on product behaviour. While the justification of such wider specifications may be challenging from a regulatory context, approaches such as physiological-based biopharmaceutics modeling (PBBM) can be utilised for this purpose.Product DRL is a fixed-dose combination product consisting of immediate release (IR) and extended-release (ER) portions. For the ER portion, the dissolution specifications consisted of four time points, and a proposal was made to relax the specification at the 2h time point (from 50-70% to 45-67%) to reduce the batch failures at the commercial scale.To support the wider specification, a PBBM was developed and extensively validated with literature & in-house studies. Virtual bioequivalence was performed using the pivotal clinical study data.Virtual dissolution profiles for proposed wider specifications were generated using three different approaches. The incorporation of lower and upper dissolution profiles into the model indicated the absence of impact on in vivo performance thereby justifying the specifications.Regulatory acceptance of proposed specifications with PBBM indicated the significance of using modeling approaches to reduce repeated testing thereby facilitating faster approvals.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-15"},"PeriodicalIF":1.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366745","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

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 : 2024-10-10 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":"https://doi.org/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 tumors, 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 characterized 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":"1-20"},"PeriodicalIF":1.3,"publicationDate":"2024-10-10","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

Metabolism and disposition of zamicastat in rats. 扎西司他在大鼠体内的代谢和处置。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-10-10 DOI: 10.1080/00498254.2024.2411993

Francisca Araújo, Maria Luisa Dória, Alexandre Beliaev, László E Kiss, Maria João Bonifácio, Joerg Holenz, Patrício Soares-da-Silva, Ana Isabel Loureiro

{"title":"Metabolism and disposition of zamicastat in rats.","authors":"Francisca Araújo, Maria Luisa Dória, Alexandre Beliaev, László E Kiss, Maria João Bonifácio, Joerg Holenz, Patrício Soares-da-Silva, Ana Isabel Loureiro","doi":"10.1080/00498254.2024.2411993","DOIUrl":"10.1080/00498254.2024.2411993","url":null,"abstract":"The metabolism and disposition of zamicastat, a reversible dopamine β-hydroxylase (DβH) inhibitor, developed for treatment of Pulmonary Arterial Hypertension (PAH), were investigated in rats after oral and intravenous administration of [14C]-zamicastat.Zamicastat was rapidly absorbed and widely distributed to peripheral tissues, with total radioactivity almost completely recovered 168 h post-dose. Its main route of excretion was via faeces, whilst urine and expired air had minor roles.Maximum plasma concentration of zamicastat-related radioactivity occurred in the first hours, remaining quantifiable up to 144 h. The unchanged zamicastat plasma peak was 2 h post-dose and declined to low levels over 24 h.Zamicastat metabolism occurs largely during the first 8 h with only one metabolite identified in the latest time-point (96 h), the isothiocyanic acid/thiocyanic acid (tautomeric forms). Zamicastat metabolic pathway involved multiple reactions comprising desulphurisation, oxidative desulphurisation, N-debenzylation followed by further oxidation or N-acetylation, and the unexpected multistep metabolic pathway leading to isothiocyanic acid/thiocyanic acid.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"1-12"},"PeriodicalIF":1.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366746","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 pharmacokinetics of dabigatran in a rat model of hyperlipidemia induced by poloxamer 407. Poloxamer 407 诱导的大鼠高脂血症模型中达比加群的药代动力学。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-09-12 DOI: 10.1080/00498254.2024.2404168

Ji Hyeon Kim,Eugene Baek,Hee Eun Kang

{"title":"The pharmacokinetics of dabigatran in a rat model of hyperlipidemia induced by poloxamer 407.","authors":"Ji Hyeon Kim,Eugene Baek,Hee Eun Kang","doi":"10.1080/00498254.2024.2404168","DOIUrl":"https://doi.org/10.1080/00498254.2024.2404168","url":null,"abstract":"Various pharmacokinetic changes have been reported in experimental hyperlipidemic (HL) animal models. To evaluate whether P-glycoprotein (P-gp) activity was affected in HL rats, we assessed the pharmacokinetics of dabigatran after oral administration of dabigatran etexilate (DABE); this is a dabigatran prodrug and a well-known P-gp substrate.HL and control rats exhibited similar area under the plasma concentration-time curve (AUC), total body clearance (CL), and steady state volume of distribution (Vss) values following intravenous administration of dabigatran (1 mg/kg). This suggested that the distribution and elimination of dabigatran were similar in control and HL rats.The hepatic and intestinal P-gp protein levels did not differ significantly between control and HL rats. The dabigatran AUC and extent of absolute oral bioavailability (F) values were similar in control and HL rats following oral administration of DABE (10 mg/kg as dabigatran). Therefore, there was no apparent change in intestinal P-gp activity in HL rats compared to control rats.This study revealed no significant change in P-gp expression or activity in the intestine or liver of HL rats, and similar pharmacokinetics of dabigatran. Hyperlipidemia may not directly affect the oral absorption of P-gp substrate drugs.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":"12 1","pages":"1-28"},"PeriodicalIF":1.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215259","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 tyrosine kinase inhibitors used for the treatment of non-small cell lung carcinoma on cytochrome P450 2J2 activities. 用于治疗非小细胞肺癌的酪氨酸激酶抑制剂对细胞色素 P450 2J2 活性的影响。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-09-01 Epub Date: 2024-08-12 DOI: 10.1080/00498254.2024.2389401

Ayaka Kojima, Masayuki Nadai, Norie Murayama, Hiroshi Yamazaki, Miki Katoh

{"title":"Effects of tyrosine kinase inhibitors used for the treatment of non-small cell lung carcinoma on cytochrome P450 2J2 activities.","authors":"Ayaka Kojima, Masayuki Nadai, Norie Murayama, Hiroshi Yamazaki, Miki Katoh","doi":"10.1080/00498254.2024.2389401","DOIUrl":"10.1080/00498254.2024.2389401","url":null,"abstract":"Cytochrome P450 (CYP) 2J2 is responsible for the epoxidation of arachidonic acid, producing epoxyeicosatrienoic acids (EETs) that are known to enhance tumorigenesis. CYP2J2 is prominently expressed in the heart and also found in the lungs. Furthermore, the expression level of CYP2J2 in tumour tissues is higher than that in adjacent normal tissues. Non-small cell lung carcinoma is a common cancer, and tyrosine kinase inhibitors (TKIs) are powerful tools for its treatment. This study aimed to elucidate the inhibitory effects of 17 TKIs on CYP2J2 activity using LC-MS/MS.Seventeen TKIs exhibited different inhibitory effects on CYP2J2-catalysed astemizole O-demethylation in recombinant CYP2J2. Pralsetinib and selpercatinib showed strong competitive inhibition, with inhibition constant values of 0.48 and 1.1 µM, respectively. They also inhibited other CYP2J2 activities, including arachidonic acid epoxidation, hydroxyebastine carboxylation, and rivaroxaban hydroxylation.In conclusion, we showed that pralsetinib and selpercatinib strongly inhibit CYP2J2 activity. Inhibition of 14,15-EET production by these TKIs may be a novel mechanism for suppressing tumour growth and proliferation. Additionally, when these TKIs are co-administered with a CYP2J2 substrate, we may consider the possibility of drug-drug interactions via CYP2J2 inhibition.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"642-647"},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894496","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

Three methods to optimise polymyxin B dosing using estimated AUC after first dose: validation with the data generated by Monte Carlo simulation. 利用首次用药后的估计 AUC 值优化多粘菌素 B 剂量的三种方法：利用蒙特卡洛模拟生成的数据进行验证。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-09-01 Epub Date: 2024-07-08 DOI: 10.1080/00498254.2024.2370051

Qingxia Liu, Jianxing Zhou, You Zheng, Baohua Xu, Dandan Li, Maobai Liu, Xiaohan Zhang, Xuemei Wu

{"title":"Three methods to optimise polymyxin B dosing using estimated AUC after first dose: validation with the data generated by Monte Carlo simulation.","authors":"Qingxia Liu, Jianxing Zhou, You Zheng, Baohua Xu, Dandan Li, Maobai Liu, Xiaohan Zhang, Xuemei Wu","doi":"10.1080/00498254.2024.2370051","DOIUrl":"10.1080/00498254.2024.2370051","url":null,"abstract":"To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUCSS,24h) using limited concentrations after its first dose.Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUCSS,24h was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula.In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -8.73%, 1.37%, and -0.48%, respectively. The corresponding value was -11.15%, 1.99%, and -0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -12.63%, -6.47%, and -0.54% when the sampling time shifted.The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"615-623"},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331920","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

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