Drug Metabolism and Pharmacokinetics最新文献

英文中文

Metabolism of simvastatin by Streptomyces griseolus CYP105A1 and its variants for the production of human simvastatin metabolites 灰色链霉菌CYP105A1及其变异对辛伐他汀的代谢及其对人类辛伐他汀代谢物的产生

IF 2.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-10-24 DOI: 10.1016/j.dmpk.2025.101506

Sachiyo Yoneda , Kaori Yasuda , Bunzo Mikami , Teisuke Takita , Kiyoshi Yasukawa , Masahiro Hamada , Hiromasa Imaishi , Toshiyuki Sakaki , Shinichi Ikushiro

Streptomyces griseolus CYP105A1 showed hydroxylation activity at 25- and 1α-positions of vitamin D₃ to produce an active form of vitamin D₃. We have succeeded in dramatically increasing its activity by site-directed mutagenesis. We also found that CYP105A1 and its mutants metabolize various non-steroidal anti-inflammatory drugs. In this study, we attempted to metabolize simvastatin (SV), an HMG-CoA reductase inhibitor, by CYP105A1 mutants, and compared their metabolism with that by human CYP3A4. The SV was converted into multiple metabolites by the CYP105A1 variants CYP105A1-R84A and CYP105A1-R84A/M239A, with the latter exhibiting significantly higher activity than the former. The metabolites were estimated to be 6′-hydroxy-SV, 3′-hydroxy-SV, 3″-hydroxy SV, 3′,5′-dihydrodiol SV, and 6′-exomethylene SV. In addition, 6′-hydroxy-SV was non-enzymatically converted to 3′-hydroxy-SV under acidic conditions. The X-ray crystal structure of SV-bound CYP105A1-R84A suggested the formation of a 3′,4′-epoxide intermediate, from which 3′-hydroxy and 3′,5′-dihydrodiol SV were presumed to be generated non-enzymatically. It is noted that all of these metabolites have either been reported as SV metabolites formed by human CYP3A4 or were detected in the present study. Thus, CYP105A1-R84A/M239A appears to be highly useful for the production of human metabolites of SV.

灰色链霉菌CYP105A1在维生素D3的25-和1α-位点显示羟基化活性，产生活性形式的维生素D3。我们已经成功地通过定点诱变极大地增加了它的活性。我们还发现CYP105A1及其突变体代谢各种非甾体抗炎药。在本研究中，我们试图通过CYP105A1突变体代谢HMG-CoA还原酶抑制剂辛伐他汀（SV），并将其与人类CYP3A4的代谢进行比较。SV被CYP105A1变异CYP105A1- r84a和CYP105A1- r84a /M239A转化为多种代谢物，后者的活性明显高于前者。代谢产物估计为6 ' -羟基SV， 3 ' -羟基SV， 3″-羟基SV， 3 ',5 ' -二氢二醇SV和6 ' -外甲基SV。此外，6′-羟基- sv在酸性条件下非酶转化为3′-羟基- sv。SV结合的CYP105A1-R84A的x射线晶体结构表明形成了一个3 ',4 ' -环氧化物中间体，由此推定3 ' -羟基和3 ',5 ' -二氢二醇SV是非酶促生成的。值得注意的是，所有这些代谢物要么被报道为人类CYP3A4形成的SV代谢物，要么在本研究中被检测到。因此，CYP105A1-R84A/M239A似乎对人体SV代谢产物的产生非常有用。

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引用次数: 0

Japanese medicinal drug labeling for use in the clinical setting as informed by pharmacogenomic data on cytochrome P450 enzymes obtained from in silico studies. 根据从计算机研究中获得的细胞色素P450酶的药物基因组学数据，用于临床环境的日本药品标签。

IF 2.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-10-01 Epub Date: 2025-05-29 DOI: 10.1016/j.dmpk.2025.101496

Yoichi Tanaka, Makiko Shimizu, Yoshiro Saito, Hiroshi Yamazaki

Although the United States Food and Drug Administration has disclosed a list of drugs with pharmacogenomic biomarkers for drug labeling, there is limited information regarding pharmacogenomic-associated drugs in Japan. Such associations include genetic variants of uridine diphosphate glucuronosyltransferase 1A1 for irinotecan, nudix hydrolase 15 for thiopurine drugs, and cytochrome P450 (P450) 2C9 for siponimod. The effects of such genetic variants on drug concentrations are similar to those from drug interactions. Because of race and dosage differences, the relevance of pharmacogenomic associations in Asian populations requires confirmation. This white paper proposes that in vitro pharmacogenomic information can be used to predict human pharmacokinetics and to describe in drug labels the changes in blood concentrations by genetic variants. For P450 variants CYP2C9∗3, CYP2C19∗2, CYP2C19∗3, CYP2D6∗10, and CYP3A4∗16, we propose using the enzymatic activity parameters obtained from in vitro functional analysis of the drug-metabolizing enzymes for multiple substrate drugs to predict the effects of these variants on human pharmacokinetics. Consequently, in patients prescribed only a single drug, anything more than a "moderate effect" on plasma exposure should be mentioned as a caution in the drug labels; such effects are likely caused by enzyme polymorphisms resulting in similar effects to drug-drug interactions.

尽管美国食品和药物管理局已经公布了一份药物标签上带有药物基因组生物标记物的药物清单，但在日本，关于药物基因组相关药物的信息有限。这些关联包括伊立替康的尿苷二磷酸葡萄糖醛基转移酶1A1、硫嘌呤类药物的嘌呤水解酶15和西泊尼莫德的细胞色素P450 (P450) 2C9的遗传变异。这些基因变异对药物浓度的影响与药物相互作用的影响相似。由于种族和剂量的差异，亚洲人群中药物基因组关联的相关性需要证实。本白皮书提出体外药物基因组学信息可用于预测人体药代动力学，并在药物标签上描述遗传变异引起的血药浓度变化。对于P450变体CYP2C9∗3，CYP2C19∗2,CYP2C19∗3，CYP2D6∗10和CYP3A4∗16，我们建议使用从多种底物药物代谢酶的体外功能分析中获得的酶活性参数来预测这些变体对人体药代动力学的影响。因此，对于只服用一种药物的患者，任何对血浆暴露超过“中等影响”的情况都应在药物标签上注明注意事项；这种影响可能是由酶多态性引起的，导致类似于药物-药物相互作用的影响。

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引用次数: 0

Important role of OATP in the liver disposition of ezetimibe and its consequent glucuronidation metabolite OATP在依泽可米及其后续糖醛酸化代谢产物的肝脏处理中的重要作用。

IF 2.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-09-18 DOI: 10.1016/j.dmpk.2025.101503

Ying Su , Xinyi Zhang , Yiguo Jiang , Cheng Wang , Jianqing Ruan

Ezetimibe is a widely used antilipemic agent that lowers LDL-C and raises HDL-C by inhibiting intestinal cholesterol absorption. However, the mechanisms governing the hepatic transport of ezetimibe and its glucuronide metabolite remain unclear. In this study, we demonstrated that ezetimibe is rapidly metabolized to its glucuronide in mouse, rat, and human liver microsomes, with UGT1A1 showing the highest catalytic activity, followed by UGT1A3. In vitro transport assays revealed that human OATP1B1 and OATP1B3 selectively mediate the uptake of ezetimibe-glucuronide, but not parent ezetimibe. Using Slco1b2 knockout mice, an in vivo model for hepatic OATP deficiency, we found that knockout significantly increased the plasma AUC and decreased the liver-to-plasma ratio of ezetimibe-glucuronide, without affecting parent ezetimibe. These results indicate that OATP-mediated hepatic uptake is key to the disposition of ezetimibe-glucuronide, which may influence the pharmacokinetics and clinical efficacy of ezetimibe.

依折替米贝是一种广泛使用的降脂剂，通过抑制肠道胆固醇吸收来降低LDL-C和升高HDL-C。然而，依折麦布及其葡萄糖醛酸代谢产物的肝脏转运机制尚不清楚。在本研究中，我们证明依折麦比在小鼠、大鼠和人的肝微粒体中被快速代谢为葡萄糖醛酸盐，其中UGT1A1的催化活性最高，其次是UGT1A3。体外转运实验显示，人OATP1B1和OATP1B3选择性地介导依zetimibe-glucuronide的摄取，而不是亲本依zetimibe。使用肝脏OATP缺乏的体内模型Slco1b2敲除小鼠，我们发现敲除显著增加血浆AUC，降低依zetimibe-glucuronide的肝-血浆比值，而不影响亲本依zetimibe。这些结果表明ooatp介导的肝脏摄取是依zetimibe-glucuronide处置的关键，可能影响依zetimibe的药代动力学和临床疗效。

引用次数: 0

Tyrosine kinase inhibitors, nilotinib and radotinib, suppress both catalytic function and mRNA expression of human cytochrome P450 2J2 and 2C8 酪氨酸激酶抑制剂尼罗替尼和拉多替尼抑制人细胞色素P450 2J2和2C8的催化功能和mRNA表达

IF 2.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-08-29 DOI: 10.1016/j.dmpk.2025.101501

Ayaka Kojima , Masayuki Nadai , Hiroshi Yamazaki , Miki Katoh

Cytochrome P450 (P450 or CYP) 2J2, which metabolizes exogenous medicines and endogenous arachidonic acid to 14,15-epoxyeicosatrienoic acid (14,15-EET), is expressed in various organs and cancer cells. Additionally, CYP2C8 catalyzes the synthesis of 14,15-EET, a vasodilator that promotes cancer cell proliferation. However, the effect of tyrosine kinase inhibitors (TKIs) used in leukemia treatment on CYP2J2 and CYP2C8 remains unclear. This study investigated the effects of 16 TKIs used for leukemia treatment on recombinant CYP2J2-and CYP2C8-mediated processes. Among the TKIs, nilotinib and radotinib strongly inhibited CYP2J2-dependent astemizole O-demethylation and rivaroxaban hydroxylation, and CYP2C8-mediated paclitaxel 6α-hydroxylation (<20 %), with competitive inhibition constants of 0.41 and 0.22 μM, respectively (for astemizole O-demethylation). Nilotinib and radotinib suppressed CYP2J2-and CYP2C8-catalyzed arachidonic acid epoxidation and decreased their mRNA expression in Huh-7 cells (possibly via the peroxisome proliferator-activated receptor α pathway). Given that their inhibition constants are lower than their reported plasma concentrations, both may substantially suppress CYP2J2 and CYP2C8 functional enzyme levels and enzymatic activities in clinical settings. This suppression could potentially alter vasodilation by affecting 14,15-EET production, influencing CYP2J2 and CYP2C8-mediated drug-disease (conditions) and drug-drug interactions.

细胞色素P450 (P450或CYP) 2J2在各器官和癌细胞中表达，将外源性药物和内源性花生四烯酸代谢为14,15-环氧二碳三烯酸（14,15- eet）。此外，CYP2C8催化1415 - eet的合成，1415 - eet是一种促进癌细胞增殖的血管扩张剂。然而，用于白血病治疗的酪氨酸激酶抑制剂（TKIs）对CYP2J2和CYP2C8的影响尚不清楚。本研究探讨了16种用于白血病治疗的TKIs对重组cyp2j2和cyp2c8介导过程的影响。在TKIs中，尼罗替尼和拉多替尼对cyp2j2依赖性阿司咪唑o -去甲基化和利伐沙班羟化，以及cyp2c8介导的紫杉醇6α-羟化具有较强的抑制作用（< 20%），竞争抑制常数分别为0.41 μM和0.22 μM（对阿司咪唑o -去甲基化）。尼罗替尼和拉多替尼抑制了cyp2j2和cyp2c8催化的花生四烯酸环氧化，并降低了Huh-7细胞中它们的mRNA表达（可能通过过氧化物酶体增殖物激活受体α途径）。鉴于它们的抑制常数低于其报道的血浆浓度，两者都可能在临床环境中实质性地抑制CYP2J2和CYP2C8功能酶水平和酶活性。这种抑制可能通过影响14,15- eet的产生，影响CYP2J2和cyp2c8介导的药物-疾病（状况）和药物-药物相互作用来潜在地改变血管舒张。

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引用次数: 0

L-Type amino acid transporter 1-mediated developmental change of cerebral gabapentin distribution across the rat blood-brain barrier l型氨基酸转运蛋白1介导的脑加巴喷丁血脑屏障分布的发育变化。

IF 2.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-08-29 DOI: 10.1016/j.dmpk.2025.101502

Hiroki Endo , Takeshi Sugouchi , Otaro Kobayashi , Yuma Tega , Yoshiyuki Kubo , Ken-ichi Hosoya , Shin-ichi Akanuma

Gabapentin is an anticonvulsant used in the pharmacotherapy of pediatric epilepsy. Differences in transporter-mediated cerebral drug/compound distribution across the blood-brain barrier (BBB) have been reported between neonates/infants, and adults. The purpose of our study was to comprehensively elucidate the transport of gabapentin across the BBB during childhood and its regulatory molecular systems. The cerebral distribution of [³H]gabapentin in 7-day-old rats was significantly lower than that in 42-day-old adult rats, suggesting weaker gabapentin transport in the BBB of neonates/infants than in adults. In vivo brain uptake and in vitro transport studies have indicated the involvement of transporters that accept large neutral amino acids in the cerebral gabapentin distribution across the BBB. In particular, an in vitro study using RNA interference suggested a major contribution of L-type amino acid transporter 1 (LAT1) to gabapentin transport across the BBB. In the brains of 7-day-old rats, the mRNA expression of LAT1 and the heavy chain of the 4F2 antigens (4F2hc), which forms a complex with LAT1, was reduced compared to that of 42-day-old rats. Consequently, it is suggested that a decrease in gabapentin distribution to the brain across the BBB contributes to the transcriptional reduction of cerebral LAT1 and 4F2hc.

加巴喷丁是一种用于小儿癫痫药物治疗的抗惊厥药。转运体介导的脑药物/化合物在血脑屏障（BBB）中的分布在新生儿/婴儿和成人之间存在差异。我们研究的目的是全面阐明儿童时期加巴喷丁在血脑屏障中的转运及其调控分子系统。加巴喷丁[3H]在7日龄大鼠脑内的分布明显低于42日龄成年大鼠，表明新生儿/婴儿加巴喷丁在血脑屏障中的转运比成人弱。体内脑摄取和体外转运研究表明，接受大量中性氨基酸的转运体参与了加巴喷丁在脑血脑屏障中的分布。特别是，一项使用RNA干扰的体外研究表明，l型氨基酸转运蛋白1 （LAT1）对加巴喷丁在血脑屏障中的转运起着重要作用。在7日龄大鼠的大脑中，与42日龄大鼠相比，LAT1和与LAT1形成复合物的4F2抗原重链（4F2hc）的mRNA表达减少。因此，这表明加巴喷丁在脑血脑屏障中的分布减少有助于大脑LAT1和4F2hc的转录减少。

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引用次数: 0

Construction of refined CYP2D6-Template system for studies of its metabolism and inhibition 精制cyp2d6 -模板体系的构建及其代谢和抑制研究

IF 2.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-08-01 DOI: 10.1016/j.dmpk.2025.101499

Yasushi Yamazoe , Norie Murayama , Kouichi Yoshinari

The previously reported Template system for the prediction of human CYP2D6-mediated reactions (Drug Metab Dispos 40 486-96, 2012) has been refined with the introduction of ideas of allowable width, Trigger∗-residue and the residue-initiated movement of ligands in the active site. These ideas are in common with published Template systems for human CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2E1, CYP2J2, and CYP3A4/5/7 (Drug Metab Pharmacokinet 2016, 2019, 2020, 2021, 2022, 2023, and 2024, Food Safety 2024). Total 616 reactions of 441 distinct chemicals reported as CYP2D6 ligands were examined in the refined CYP2D6-Template system. From their placements on the refined Template and rules for interaction modes, verifications of good and poor substrates, regio/stereo-selectivity, and inhibition became faithfully available for these ligands. A comparison of the placements suggested key interactions with Shelf and Left-end for ligand accommodations on the refined CYP2D6-Template. Shelf-surrounding of ligands was also proposed as a cause of their intense inhibitions. The refined CYP2D6-Template system will thus offer reliable estimations of this human CYP catalyses toward ligands of diverse structures, together with their deciphering information to lead to judgments of regioselective metabolisms.

先前报道的用于预测人类cyp2d6介导反应的模板系统（Drug Metab Dispos 40 486-96, 2012）已经通过引入允许宽度，触发*残基和残基引发的配体在活性位点的运动的想法进行了改进。这些想法与已发布的人类CYP1A1、CYP1A2、CYP2B6、CYP2C8、CYP2C9、CYP2C18、CYP2C19、CYP2E1、CYP2J2和CYP3A4/5/7模板系统相同（Drug Metab Pharmacokinet 2016、2019、2020、2021、2022、2023和2024，食品安全2024）。在精炼的CYP2D6-模板体系中，共检测了441种不同化学物质作为CYP2D6配体的616种反应。根据它们在精制模板上的位置和相互作用模式的规则，这些配体的良好和不良底物、区域/立体选择性和抑制性的验证变得忠实地可用。放置位置的比较表明，在改进的CYP2D6-Template上，与Shelf和左端进行配体安置的关键相互作用。配体的架子包围也被认为是它们具有强烈抑制作用的原因。因此，改进的CYP2D6-Template系统将提供可靠的估计，这种人类CYP催化剂对不同结构的配体，连同他们的破译信息，导致判断区域选择性代谢。

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引用次数: 0

Impact of degradation in subcutaneous tissue and lymphatic fluid on absorption of Fc-fusion proteins following subcutaneous administration 皮下给药后皮下组织和淋巴液降解对fc融合蛋白吸收的影响

IF 2.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-07-17 DOI: 10.1016/j.dmpk.2025.101500

Miki Yokoyama, Eiko Suzuki, Daisuke Nakai

Subcutaneous administration is widely used as a clinical administration route for Fc-fusion proteins. However, predicting bioavailability (BA) in humans after subcutaneous administration is challenging due to multiple factors involved in the absorption process. This study aimed to elucidate the impact of degradation on the BA of Fc-fusion proteins. We established two measurement methods for each Fc-fusion protein: the Fc/Fc method, which recognizes the Fc region; and the Protein/Fc method, which recognizes both protein and Fc region. BA of dulaglutide and romiplostim in rats were 80.1 % and 99.4 % by the Fc/Fc method, and 35.0 % and 55.5 % by the Protein/Fc method, respectively. The lower BA with the Protein/Fc method indicates that the protein region undergoes degradation during the absorption process. In stability studies with rat skin homogenates and lymphatic fluid, degradation of the protein region for both dulaglutide and romiplostim was confirmed, which was inhibited by protease inhibitors. In contrast, abatacept and etanercept were stable in skin homogenates and lymphatic fluid, and their BA in rats were comparable between the Fc/Fc and Protein/Fc methods. This study indicates that the presence or absence of protease-mediated degradation during the absorption process is one of the factors affecting the BA of Fc-fusion proteins.

皮下给药作为fc融合蛋白的临床给药途径被广泛使用。然而，由于吸收过程中涉及多种因素，预测皮下给药后人体的生物利用度（BA）具有挑战性。本研究旨在阐明降解对fc融合蛋白BA的影响。我们建立了两种检测Fc融合蛋白的方法：识别Fc区域的Fc/Fc方法；以及同时识别蛋白质和Fc区域的蛋白质/Fc方法。用Fc/Fc法测定大鼠dulaglutide和romiplostim的BA分别为80.1%和99.4%，用Protein/Fc法测定大鼠BA分别为35.0%和55.5%。蛋白质/Fc法的低BA表明蛋白质区域在吸收过程中发生了降解。在大鼠皮肤匀浆和淋巴液的稳定性研究中，证实了dulaglutide和romiplostim的蛋白区降解，蛋白酶抑制剂抑制了这种降解。相比之下，阿巴接受和依那西普在皮肤匀浆和淋巴液中是稳定的，它们在大鼠中的BA在Fc/Fc和蛋白质/Fc方法中是相当的。本研究表明，在吸收过程中是否存在蛋白酶介导的降解是影响fc融合蛋白BA的因素之一。

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引用次数: 0

Investigation of an OATP1B inhibitory effect by a cyclic peptide using the endogenous biomarker coproporphyrin-I in monkeys 利用内源性生物标志物coproporphyrin-I研究环肽对猴子OATP1B的抑制作用

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-06-03 DOI: 10.1016/j.dmpk.2025.101497

Hiromi Sawada , Yasuto Kido , Makoto Iwasaki , Kimiko Nishida , Kei Mayumi , Ryosuke Watari

Peptide drugs are expected to be a new modality that will replace traditional small molecule drugs. As the number of approved peptide drugs increases, they are being co-administered with various drugs, but there is a limited number of reports on their drug-drug interaction (DDI) in both in vitro and in vivo (clinical) studies. In this study, we investigated the transporter inhibitory potential of Compound A, a macrocyclic peptide (3.5 kDa) for the treatment of pain. We found that Compound A exhibited a strong inhibitory effect on the organic anion transporting polypeptide (OATP) 1B in an in vitro study. To assess the in vivo OATP1B inhibitory potential, Compound A was intravenously or subcutaneously administered to monkeys, and the plasma concentration of coproporphyrin-I (CP-I), an endogenous biomarker of OATP1B, was determined. Compound A markedly increased the CP-I concentration in monkeys. A semi-mechanistic pharmacokinetic model analysis using the CP-I concentration revealed that Compound A is a highly potent in vivo OATP1B inhibitor (in vivo K_{i, OATP1B}: 59.9 ng/mL as total plasma concentration). Our findings suggest that even peptides with a large molecular weight can cause DDI. These results offer valuable information for the further development of DDI guidelines for peptides.

肽类药物有望成为替代传统小分子药物的一种新形态。随着批准的多肽药物数量的增加，它们正在与各种药物共同给药，但在体外和体内（临床）研究中，关于它们的药物相互作用（DDI）的报道有限。在这项研究中，我们研究了化合物A的转运蛋白抑制电位，化合物A是一种大环肽（3.5 kDa），用于治疗疼痛。我们在体外研究中发现化合物A对有机阴离子转运多肽（OATP） 1B具有较强的抑制作用。为了评估体内对OATP1B的抑制潜力，我们将化合物A静脉注射或皮下注射给猴，并测定了OATP1B内源性生物标志物co - proporphyrin- i （CP-I）的血浆浓度。化合物A显著提高了cp - 1在猴子体内的浓度。利用cp - 1浓度的半机械药代动力学模型分析显示，化合物A是一种高效的体内OATP1B抑制剂（体内Ki， OATP1B: 59.9 ng/mL作为总血浆浓度）。我们的研究结果表明，即使是分子量较大的肽也能引起DDI。这些结果为进一步制定多肽DDI指南提供了有价值的信息。

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引用次数: 0

Development of an in vitro Metabolic Dysfunction-Associated Steatohepatitis (MASH) model to study hepatic transporters 建立体外代谢功能障碍相关脂肪性肝炎（MASH）模型研究肝脏转运体

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101123

Sarina Kyburz , William A. Murphy , Thomas Kralj , John K. Fallon , Jacqueline B. Tiley , Kim L.R. Brouwer

引用次数: 0

Development and qualification of an in vitro assay to determine target mediated internalization of TREM2 receptor specific antibodies for TMDD assessment 开发和鉴定用于TMDD评估的TREM2受体特异性抗体靶介导内化的体外测定方法

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Drug Metabolism and Pharmacokinetics

Pub Date : 2025-06-01 DOI: 10.1016/j.dmpk.2025.101134

Thomas Kraft , Anna-Lena Bolender , Aman Padamsey , Erich Koller , Markus Britschgi , Jens Niewoehner , Hans Peter Grimm

引用次数: 0

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