Xenobiotica最新文献_第2页

Potential influence of interleukin-6 -174G/C gene polymorphism on kidney graft function and tacrolimus dose requirements: five-year follow-up. 白细胞介素-6 -174G/C基因多态性对肾移植功能和他克莫司剂量需求的潜在影响：五年随访。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-10-01 Epub 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":"855-863"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","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 : 2024-10-01 Epub 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":"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":"831-839"},"PeriodicalIF":1.3,"publicationDate":"2024-10-01","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

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

Qualitative and quantitative status of cytochrome P450s after the administration of a liposomal platelet substitute in rat liver. 在大鼠肝脏中施用脂质体血小板替代物后细胞色素 P450s 的定性和定量状况。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-09-01 Epub Date: 2024-08-09 DOI: 10.1080/00498254.2024.2385535

Kazuaki Taguchi, Mai Hashimoto, Masahiro Tokuno, Shinji Takeoka, Toru Maruyama, Keishi Yamasaki, Masaki Otagiri

{"title":"Qualitative and quantitative status of cytochrome P450s after the administration of a liposomal platelet substitute in rat liver.","authors":"Kazuaki Taguchi, Mai Hashimoto, Masahiro Tokuno, Shinji Takeoka, Toru Maruyama, Keishi Yamasaki, Masaki Otagiri","doi":"10.1080/00498254.2024.2385535","DOIUrl":"10.1080/00498254.2024.2385535","url":null,"abstract":"In the process of the drug development, studies on the cytochrome P450 (CYP) profiles after its administration provided fundamental information regarding drug interactions with concomitantly administered drugs. Here, we evaluated the influence of the administration of H12-(ADP)-liposomes, a platelet substitute, on the mRNA and protein expression, and metabolic activity of CYPs, with focus on the CYP1A2, CYP2C11 and CYP3A2, in rat liver.At 24 h after administering saline or H12-(ADP)-liposomes (10 mg of lipids/kg), a quantitative RT-PCR and western blot analysis revealed that the mRNA and proteins expression of all of the target hepatic CYP isoforms were not different between the saline and H12-(ADP)-liposome groups. Furthermore, an ex vivo CYP metabolic activity assay showed that hepatic CYP metabolic activities in the H12-(ADP)-liposome group were comparable to the corresponding saline group. On the other hand, the area under the blood concentration-time curve for substitutes for CYP1A2 and CYP2C11 was higher in H12-(ADP)-liposome group than in saline group, but the degree of elevations was negligible levels.At a minimum, based on these results, we conclude that H12-(ADP)-liposomes have no quantitative and qualitative effect on the hepatic CYP isoforms, indicating that the drug interactions of H12-(ADP)-liposomes with CYP-metabolizing drugs would be negligible.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"624-628"},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861103","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

How predictive are isolated perfused liver data of in vivo hepatic clearance? A meta-analysis of isolated perfused rat liver data. 离体灌注肝脏数据对体内肝清除率的预测性如何？离体灌注大鼠肝脏数据的荟萃分析。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-09-01 Epub Date: 2024-09-23 DOI: 10.1080/00498254.2024.2404170

Julia A Schulz Pauly, J Cory Kalvass

{"title":"How predictive are isolated perfused liver data of in vivo hepatic clearance? A meta-analysis of isolated perfused rat liver data.","authors":"Julia A Schulz Pauly, J Cory Kalvass","doi":"10.1080/00498254.2024.2404170","DOIUrl":"10.1080/00498254.2024.2404170","url":null,"abstract":"Isolated perfused rat liver (IPRL) experiments have been used to answer clearance-related questions, including evaluating the impact of pathological and physiological processes on hepatic clearance (CLH). However, to date, IPRL data has not been evaluated for in vivo CLH prediction accuracy.In addition to a detailed overview of available IPRL literature, we present an in-depth analysis of the performance of IPRL in CLH prediction.While the entire dataset poorly predicted CLH (GAFE = 3.2; 64% within 3-fold), IPRL conducted under optimal experimental conditions, such as in the presence of plasma proteins and with a perfusion rate within 2-fold of physiological liver blood flow and corrected for unbound fraction in the presence of red blood cells, can accurately predict rat CLH (GAFE = 2.0; 78% within 3-fold). Careful consideration of experimental conditions is needed to allow proper data analysis.Further, isolated perfused liver experiments in other species, including human livers, may allow us to address the current in vitro-in vivo disconnects of hepatic metabolic clearance and improve our methodology for CLH predictions.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"658-669"},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296724","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

Teratogenicity is more likely a function of primary and secondary pharmacology than caused by chemically reactive metabolites: a critical evaluation of 40 years of scientific research. 致畸性更可能是原发性和继发性药理作用的结果，而不是化学反应代谢物造成的：对 40 年科学研究的批判性评估。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-09-01 Epub Date: 2024-07-01 DOI: 10.1080/00498254.2024.2366302

Dennis A Smith

引用次数: 0

Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of [¹⁴C]aficamten following single oral dose administration to rats. 大鼠单次口服[14C]Aficamten 的药代动力学、质量平衡、组织分布、代谢和排泄。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-09-01 Epub Date: 2024-08-07 DOI: 10.1080/00498254.2024.2381111

Mark P Grillo, Rajaa Sukhun, Mohammad Bashir, Luke Ashcraft, Bradley P Morgan

{"title":"Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of [14C]aficamten following single oral dose administration to rats.","authors":"Mark P Grillo, Rajaa Sukhun, Mohammad Bashir, Luke Ashcraft, Bradley P Morgan","doi":"10.1080/00498254.2024.2381111","DOIUrl":"10.1080/00498254.2024.2381111","url":null,"abstract":"The pharmacokinetics, metabolism, excretion, mass balance, and tissue distribution of [14C]aficamten were evaluated following oral administration of an 8 mg/kg dose in Sprague Dawley rats and in a quantitative whole-body autoradiography study in Long Evans rats.[14C]Aficamten accounted for ∼80% and a hydroxylated metabolite (M1) accounted for ∼12% of total radioactivity in plasma over 48-h (AUC0-48). Plasma tmax was 4-h and the t1/2 of total plasma radioactivity was 5.8-h.Tissues showing highest Cmax exposures were myocardium and semitendinosus muscle.Most [14C]aficamten-derived radioactivity was excreted within 48-h post-administration. Mean cumulative recovery in urine and faeces over 168-h was 8.3% and 90.7%, respectively.In urine and bile, unchanged aficamten was detected at <0.1 and <0.2% of dose, respectively; however, based on total radioactivity excreted in urine (8.0%) and bile (51.7%), approximately 60% of dose was absorbed.[14C]Aficamten was metabolised by hydroxylation with subsequent glucuronidation where the most abundant metabolite recovered in bile was M5 (35.2%), the oxygen-linked glucuronide of hydroxylated aficamten (M1a). The major metabolite detected in faeces was a 1,2,4-oxadiazole moiety ring-cleaved metabolite (M18, 35.3%), shown to be formed from the metabolism of M5 in incubations with rat intestinal contents solution.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"670-685"},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767605","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

Prediction of human serum concentration-time profiles of therapeutic monoclonal antibodies using common marmosets (Callithrix jacchus): initial assessment with canakinumab, adalimumab, and bevacizumab. 利用普通狨猴（Callithrix jacchus）预测治疗性单克隆抗体的人血清浓度-时间曲线：对卡那单抗、阿达木单抗和贝伐珠单抗的初步评估。

IF 1.3 4区医学

Xenobiotica Pub Date : 2024-09-01 Epub Date: 2024-07-26 DOI: 10.1080/00498254.2024.2371921

Ayaka Tajiri, Shogo Matsumoto, Satoshi Maeda, Takuma Soga, Kensuke Kagiyama, Hiroshi Ikeda, Kazumasa Fukasawa, Atsunori Miyata, Hidetaka Kamimura

{"title":"Prediction of human serum concentration-time profiles of therapeutic monoclonal antibodies using common marmosets (Callithrix jacchus): initial assessment with canakinumab, adalimumab, and bevacizumab.","authors":"Ayaka Tajiri, Shogo Matsumoto, Satoshi Maeda, Takuma Soga, Kensuke Kagiyama, Hiroshi Ikeda, Kazumasa Fukasawa, Atsunori Miyata, Hidetaka Kamimura","doi":"10.1080/00498254.2024.2371921","DOIUrl":"10.1080/00498254.2024.2371921","url":null,"abstract":"Cynomolgus monkeys and human FcRn transgenic mice are generally used for pharmacokinetic predictions of therapeutic monoclonal antibodies (mAbs). In the present study, the application of the common marmoset, a small nonhuman primate, as a potential animal model for prediction was evaluated for the first time.Canakinumab, adalimumab, and bevacizumab, which exhibited linear pharmacokinetics in humans, were selected as the model compounds. Marmoset pharmacokinetic data were reportedly available only for canakinumab, and those for adalimumab and bevacizumab were acquired in-house.Four pharmacokinetic parameters for a two-compartment model (i.e. clearance and volume of distribution in the central and peripheral compartments) in marmosets were extrapolated to the values in humans with allometric scaling using the average exponents of the three mAbs. As a result, the observed human serum concentration-time curves of the three mAbs following intravenous administration and those of canakinumab and adalimumab following subcutaneous injections (with an assumed absorption rate constant and bioavailability) were reasonably predicted.Although further prediction studies using a sufficient number of other mAbs are necessary to evaluate the versatility of this model, the findings indicate that marmosets can be an alternative to preceding animals for human pharmacokinetic predictions of therapeutic mAbs.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"648-657"},"PeriodicalIF":1.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559907","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