从“守门人”到“引路人”，药明康德DMPK的二十载创新之路 | Bilingual

编者按：“让天下没有难做的药，难治的病”，是初心，更是愿景。自成立以来，药明康德步履不停：从一间实验室，到覆盖亚洲、欧洲和北美的全球网络。从早期的化学合成服务，到贯穿研究（R）、开发（D）和生产（M）的一体化平台。从第一位客户，到全球三十多个国家的众多合作伙伴。不断发展的，是规模与能力；始终坚守的，是梦想与承诺。本系列文章将立足药明康德一体化CRDMO平台，系统讲述公司不断深化的能力和规模体系，以平台承载信任，持续赋能客户创新，共同推动更多突破性疗法走向病患。

一款药物在发挥药效之前，会在人体内经历一段神奇而关键的旅程：吸收、分布、代谢与排泄。这一过程虽无形，却对药效与安全性至关重要。为了系统揭示这一内在规律，让它能够在我们眼前“具象化”，药物代谢与药代动力学（DMPK）研究应运而生。

2026年，药明康德药物代谢与动力学部（下称“药明康德DMPK”）迎来了成立的第二十个年头。站在这一里程碑回望，我们不仅见证了学科本身的演进，更亲历了DMPK在药物研发体系中角色的深刻蜕变。曾经，DMPK只是研发流程中的一道检验“关卡”；如今，它已升级为驱动早期研发决策的核心“引擎”之一。二十年来，药明康德DMPK与行业创新同频共振，深度参与了新药从设计、优化到临床转化的全过程。

守正启新：药明康德DMPK伴随药物发现演进而成长

药明康德DMPK致力于将药代动力学洞察贯穿研发全链条，助力全球合作伙伴在候选药物的分子设计、结构优化与临床推进中更具底气与信心。二十载深耕笃行，药明康德DMPK已从传统的描述评估角色，升级为深度嵌入新药研发全程的技术平台。它通过系统解析化合物的吸收、分布、代谢、排泄特征，为候选分子的筛选及优化方向提供关键支撑。

这一变化不仅体现在科学进步上，更带来了研发效率的显著提升。当前全球新药开发临床成功率仍维持在10%-12%，但导致项目失败的核心原因已发生根本性改变。历史上，药代动力学性质不佳和生物利用度低曾导致约40%的研发折戟，如今，这一比例已降至个位数[1,2]。这一转变主要得益于DMPK更早、更系统地融入了药物发现流程，也标志着行业从“被动评估”迈向“主动设计”——在候选分子步入临床阶段之前，就能洞悉其在体内的行为轨迹。

图片来源：123RF

如今，DMPK已前置到分子设计源头。它通过提供理化性质、渗透性及代谢稳定性等关键洞察，指导分子优化，从起始阶段筛选出体内表现特征更优的潜力化合物。其价值贯穿药物开发全周期：为从临床前研究到人体的转化策略提供科学依据、辅助临床剂量选择与给药方案设计、预测药物相互作用，同时也是监管申报的关键支撑。可以说，DMPK已进化为一门贯通药物发现与开发、最终惠及全球患者的综合性学科。

药明康德DMPK负责人沈良博士表示，“DMPK的真正价值，在于以临床需求为终点，理解药物的药代动力学特征及研究策略需求，通过药明康德药物代谢与动力学平台的自动化及智能化平台和药代领域专业团队的引领，助推客户将药物更高效、更精准、更优质地抵达患者。”

在波澜壮阔的行业变革浪潮中，药明康德DMPK于2006年成立，成为药明康德全球一体化赋能平台的重要组成部分。二十年来，平台与全球新药创新同频成长、同步壮大，赋能能力从基础的实验室药代动力学检测，拓展为集体外ADME研究、体内PK研究、代谢产物鉴定、放射性标记合成及ADME研究、生物分析及临床转化于一体的全球化技术平台。如今，药明康德DMPK已在全球多地设立研究基地，并成功支持数千个IND及NDA项目顺利推进。

重塑范式：新分子涌现时代的DMPK新篇章

面对新兴治疗模式不断升级的复杂性，药明康德DMPK为下一代药物量身打造专属药代动力学策略，应对其独特研发难题，让这些药物分子能更快、更稳地来到患者身边。

如果说DMPK过往的迭代升级，得益于分析工具的革新与研究流程的整合与前置，那么其新一轮转型，则源于药物分子本质的深刻变革。肽类、寡核苷酸、抗体偶联药物、靶向蛋白降解剂、mRNA疗法与共价药物等创新分子快速崛起，打破了诸多传统药代动力学的既有认知与假设。这类分子往往突破传统“类药”分子边界，在稳定性、组织分布、载荷释放、生物分析检测等方面提出了全新挑战。为此，药明康德DMPK搭建了面向特定治疗模态的评估体系与协同平台，摒弃单一化评估框架，为每一种新分子构建专属研究方法，从而为各类新兴疗法提供全方位支撑。

以寡核苷酸疗法为例，传统分析技术已难以满足研究需求。为此，药明康德DMPK搭建了专属技术平台，将LBA分析方法与高灵敏度LC-MS/MS检测技术深度结合，实现精准定量、代谢物谱解析与组织分布研究。这一系列能力，折射出DMPK领域的重要转向：从被动适配传统范式，转向主动构建全新规则，以适配下一代创新疗法的研发需求。

再以ADC研发为例，其药效高度依赖抗体、连接子、细胞毒性载荷三大组分的协同作用，各自具备独特的药代动力学特征。通过整合一体化PK与生物分析研究策略，可同步定量总抗体、载药结合体与游离小分子毒素，从而更系统地揭示药物体内暴露、稳定性与疗效的关联。

除深度赋能单个研发项目外，药明康德DMPK更以系统化经验共享，推动全球科学共同体合力共进。依托在复杂药物领域积累的大量实战洞察，团队撰写并携手Wiley出版社出版了聚焦新型药物及疾病领域DMPK研究策略的专业专著《Drug Metabolism and Pharmacokinetics: Frontiers, Strategies, and Applications》，该书覆盖ADC、多肽、寡核苷酸等热门领域，围绕体外与体内药代动力学、代谢产物鉴定及结构优化、放射性标记合成及ADME、生物分析等核心方向，结合丰富的应用实例，构建了完整的新分子DMPK研究体系。通过开放共享知识与实战经验，药明康德DMPK在深度赋能客户的同时，更持续推动了DMPK学科在新分子大量涌现时代背景下的整体发展与演进。

智驱增效：自动化与智能化驱动的提效升质之路

近年来，自动化与智能化技术正深刻重塑药物研发范式。面对新药研发对“优质”与“快速”的双重需求，药明康德DMPK将自动化与智能化作为核心引擎，通过全方位能力建设，系统性地将“智驱增效”从理念转化为可量化的生产力。从自动化设备的多site布设与多系统软硬件的串联整合，到智能排班系统对实验流程的动态优化及高效调配，再到智能解谱平台对复杂分子结构的精准解析——药明康德DMPK构建了从实验管理到数据产出的全链条闭环，成功突破效率瓶颈，让智能化提效升质真正落地。这种底层能力的打通和提升，为全球合作伙伴缩短临床前研发周期、筑牢早期管线开发根基提供了坚实支撑。

在自动化方面，为了打破单一设备的局限，团队搭建了高通量整合型液体工作站，将体外ADME实验的各个环节无缝串联，实现流程的“一键贯通”。同时，团队成功引入高通量生物样品前处理系统Night Watcher，实现体内样品24小时连续自动化处理。这一升级在显著提升实验室产能的同时，也大幅减少了人工干预，有效避免人为误差，从而确保实验的高可重复性与数据准确性。此外，先进的化合物自动化存储系统与机器视觉技术协同，让化合物的入库、识别与盘点高效运转，构建了从接收到末端处置的全生命周期智能管理闭环。整套自动化布局理顺了样品与化合物全链路运转流程，为批量开展体外、体内成药性评价提供稳定保障。

DMPK高通量生物样品前处理系统Night Watcher

如果说自动化是“解放双手”、消解重复劳作；那么智能化便是“赋能大脑”，为复杂决策破局。面对新分子药物层出不穷、复杂结构解析难题日益凸显的挑战，药明康德DMPK前瞻性地推出了TidesID一站式化合物鉴定平台，可自动解析多肽和寡核苷酸等复杂分子结构，并精准匹配质谱数据，大幅优化项目周转时间。

智能化同样重塑着药代动力学研究的效率与精准度：药明康德DMPK打造的智能动物房，依托Resource Management System（RMS）系统、Internet of Things（IoT）平台、电子笼牌、芯片项圈四大核心技术，实现动物全生命周期精准管理、设备数据实时联动、信息秒更与个体秒识别。这有效减少了资源错配与人为误差，为复杂药物的体内研究筑牢了精准高效的底层支撑。

未来，药明康德DMPK将持续拓展数智化应用场景，以技术创新不断突破效率和交付质量的边界，为全球合作伙伴的新药研发之路保驾护航。

展望未来：二十载积淀，再启新程

2026年，药明康德DMPK迎来成立二十周年。这不仅是回望过往深耕足迹的节点，更是锚定方向、展望未来的全新契机。二十载春秋砥砺，药明康德DMPK的发展历程，始终与全球药物发现的宏大演进深度交织、同向而行。在人类追求创新药物的征程上，DMPK领域正加速演进，不仅预测愈发精准、协同走向一体，更肩负着全面赋能新药研发的重要使命。曾经主要扮演验证角色的DMPK，如今已蜕变为药物设计、优化及临床转化的核心驱动力之一。

征程万里风正劲，重任千钧再出发。随着新兴治疗模式持续拓展药物研发的边界，随着科技革新重塑新药开发全流程的决策逻辑，DMPK的角色也必将随科学演进不断迭代、焕发新的活力。对于药明康德DMPK而言，过去二十年的成就，从来不是由某一次单点突破定义，而是由持续深耕的协作精神、灵活适配的创新能力，以及全流程赋能全球合作伙伴的坚定承诺，一步步铸就。未来，或许将面临更艰巨的挑战，需要更深度的学科整合与技术创新，但初心如磐、使命不改：以更高效、更笃定的方式，助力研发更优质的药物，努力实现“让天下没有难做的药，难治的病”的共同愿景。

From Exposure to Insight:

20 Years of DMPK Innovation at WuXi AppTec

Before a medicine can change a life, it must first complete a remarkable yet critical journey, navigating absorption, distribution, metabolism, and excretion within the human body. This process, often described through drug metabolism and pharmacokinetics (DMPK), has long remained invisible yet decisive, determining the fate of drug candidates well before they reach patients.

In 2026, WuXi AppTec DMPK marks its 20th anniversary, offering a vantage point to reflect on how the discipline, as well as its role in drug discovery, has evolved. Once a checkpoint, DMPK has become an early-stage decision engine.Over the past two decades, WuXi AppTec DMPK has grown in tandem with industry innovation, deeply participating in the full journey of new drug design, optimization, and late-stage development translation.

From Gatekeeper to Guide: How WuXi AppTec DMPK Grew with the Evolution of Drug Discovery

WuXi AppTec DMPK enables global partners to design, optimize, and advance drug candidates with greater confidence by integrating pharmacokinetic insights across discovery and development. This capability has been built over two decades, evolving from a descriptive and evaluative function into a technical platform deeply embedded throughout the new drug R&D process. By systematically characterizing the absorption, distribution, metabolism, and excretion (ADME) properties of compounds, it provides critical support for the optimization and screening of candidate molecules.

This change is reflected not only in scientific advances but also in measurable improvements in R&D efficiency. While global late-stage development drug development success rates remain in the range of 10-12%, the nature of failure has shifted significantly. Historically, suboptimal pharmacokinetics and bioavailability accounted for up to 40% attrition in development[1,2].Today, that figure has declined to single digits, a change widely attributed to earlier and more systematic integration of DMPK into discovery workflows. This shift marks a transition from reactive assessment to proactive design, where understanding how a molecule behaves in the body begins well before itleaves thepreclinical stage.

Image source: 123RF

Increasingly, DMPK is embedded at the point of design. It guides molecular optimization through insights into physicochemical properties, permeability, and metabolic stability, and enables the selection of compounds with more favorable in vivo profiles from the outset. Its role extends across the development continuum. It informs translational strategies from preclinical models to humans, supports dose selection and regimen design, enables prediction of drug–drug interactions, and forms a foundational component of regulatory submissions. In this way, DMPK has evolved into an integrative science that connects discovery with development and ultimately with patients.

“The real value of DMPK lies in taking patient medication needs as the ultimate goal, understanding a drug’s pharmacokinetic profile and research strategy requirements, and leveraging WuXi AppTec’s automated and information-driven DMPK platform, alongside our team of pharmacokinetic experts, to empower clients to bring drugs to patients faster, more accurately, and with higher quality,”says Dr. Liang Shen, Head of WuXi AppTec DMPK.

Amid the sweeping transformation of the industry, WuXi AppTec DMPK was established in 2006. Over the past two decades, the platform has grown in step with the field. It has expanded from foundational laboratory pharmacokinetic capabilities into a globally integrated platform spanning in vitro ADME, in vivo PK, metabolite identification, radiolabeled synthesis and ADME, bioanalysis, and late-stage development translation. Today, WuXi AppTec DMPK has established research sites across multiple regions worldwide and, leveraging its extensive experience, successfully supports thousands of IND and NDA programs.

Redefining the Paradigm: A New Chapter for DMPK in the Era of Novel Modalities

To address the growing complexity of emerging therapeutic modalities, WuXi AppTec DMPK has developed tailored pharmacokinetic strategies that respond to the unique challenges of next-generation drug classes, ensuring these molecules reach patients faster and with greater confidence.

If the evolution of DMPK has been shaped by better tools and earlier integration, its next transformation has been driven by a more fundamental shift: the changing nature of the drug itself. The rise of novel therapeutic modalities, including peptides, oligonucleotides, antibody-drug conjugates (ADCs), targeted protein degraders, mRNA therapeutics, and covalent drugs, has challenged many of the assumptions that once defined pharmacokinetics. These molecules often extend beyond traditional “drug-like” boundaries, raising new questions around stability, tissue distribution, payload release, and bioanalytical measurement.In response, WuXi AppTec DMPK has developed modality-specific evaluation strategies and coordinated platforms, supporting a broad range of emerging therapeutic formats. Rather than applying a single framework to increasingly complex molecules, tailored methodologies have been established for each modality.

For oligonucleotide therapeutics, where traditional small-molecule assays are insufficient, specialized platforms combine LBA assays with high-sensitivity LC-MS/MS approaches. These support accurate quantification, metabolite profiling, and tissue distribution analysis. Together, these capabilities reflect a broader shift in DMPK, moving from adapting legacy paradigms to actively redefining them to meet the demands of next-generation therapeutics.

In the realm of ADC development, therapeutic behavior depends on the coordinated characterization of multiple components: the antibody, linker, and cytotoxic payload. Each has its distinct pharmacokinetic profile. Integrated PK and bioanalytical strategies enable simultaneous quantification of total antibody, conjugated payload, and released small-molecule toxins, providing a more complete understanding of exposure, stability, and efficacy.

Beyond enabling individual R&D programs, WuXi AppTec DMPK has also contributed to advancing the global scientific community by systematically sharing its accumulated experience, driving the community to move forward together.Drawing on extensive practical insights accumulated across the complex drug field, the team, in collaboration with Wiley, published the dedicated monograph Drug Metabolism and Pharmacokinetics: Frontiers, Strategies, and Applications, which focuses on DMPK research strategies for novel modalities and disease areas. Covering key sectors such as ADCs, peptides, and oligonucleotides, the book centers on core directions including in vitro and in vivo pharmacokinetics, metabolite identification and structural optimization, radiolabeled synthesis and ADME, and bioanalysis. Combined with a wealth of real-world case studies, it establishes a comprehensive new molecular DMPK research system. By openly sharing knowledge and practical experience, WuXi AppTec DMPK not only extensively supports its clients but also continuously drives the overall development and evolution of the DMPK discipline in the era of novel molecules.

Information-Driven Efficiency: Elevating Quality and Speed through Automation & Digitalization

In recent years, automation and information technologies have significantly reshaped the drug R&D paradigm.To meet the dual demands of “high-quality” and “high-speed” in new drug development, WuXi AppTec DMPK has leveraged automation and digitalization as its core engine, systematically transforming the concept of “Information-Driven Efficiency" into measurable productivity through comprehensive capability building.From deploying automated equipment across multiple sites and integrating cross-system software and hardware, to dynamically optimizing and efficiently allocating experimental workflows through information-driven scheduling systems, and to precisely analyzing complex molecular structures via the information-driven spectrum interpretation platform —— WuXi AppTec DMPK has established a full-chain closed loop from experimental management to result generation, breaking efficiency bottlenecks and making information-driven efficiency and quality improvement a reality. The advancement of core underlying capabilities provides solid backing for global partners to cut preclinical development cycles and reinforce early pipeline foundations.

In terms of automation, to break the limitations of standalone equipment, WuXi AppTec DMPK has built high-throughput integrated liquid handling workstations to seamlessly connect all stages ofin vitroADME experiments, enabling a “one-click” workflow.Meanwhile, the team introduced the Night Watcher, a high-throughput biological sample pretreatment system, enabling 24/7 automated processing of in vitro samples. This upgrade has not only significantly expanded laboratory capacity but also substantially reduced manual intervention, effectively minimizing human errors and ensuring high reproducibility and result accuracy. Furthermore, an advanced vision-based automated compound storage system streamlines compound receiving, identification, and inventory checking, creating a smart closed-loop management system covering the entire lifecycle from reception to final disposal. This integrated automation layout optimizes the full-chain workflow of samples and compounds, ensuring stable support for high-throughput in vitro and in vivo druggability assessments.

Night Watcher: DMPK Fully Automated Sample Pretreatment System

While automation liberates us from repetitive tasks, digital capabilities empower decision-making, driving breakthroughs in complex problem-solving.Facing the surge of novel molecular drugs and the growing challenges in complex structure elucidation, WuXi AppTec DMPK proactively launched TidesID, a one-stop compound identification platform.The platform can automatically analyze the structures of complex molecules, such as peptides and oligonucleotides, and accurately match them with mass spectrometry readings, greatly shortening project turnaround time.

Digital technologies are also reshaping the efficiency and accuracy of pharmacokinetic research: WuXi AppTec DMPK’s intelligent animal facility, relying on four core technologies including the Resource Management System (RMS), Internet of Things (IoT) platform, electronic cage tags, and chip collars, enables precise full-lifecycle management of animals, real-time linkage of equipment data, instant information updates and rapid individual identification. This facility effectively reduces resource misallocation and human errors, laying a solid foundation of precision and efficiency for in vivo research on complex drugs.

Moving forward, WuXi AppTec DMPK will continue to expand digital technical application scenarios, continuously pushing the boundaries of efficiency and delivery quality through technological innovation, and safeguarding the new drug development journey of global partners.

Looking Ahead: From 20 Years of Progress to the Next Chapter

As WuXi AppTec DMPK marks its 20th anniversary in 2026, the milestone offers not only a moment of reflection, but also an opportunity to look ahead. Over the past two decades, the journey has unfolded alongside the broader evolution of drug discovery. The field has become more predictive, more integrated, and more ambitious in its pursuit of new medicines. What was once a largely observational discipline primarily playing a validation role has evolved into one of the key contributors to how drugs are designed, optimized, and translated to patients.

Yet, the trajectory is far from complete. As novel modalities continue to push the boundaries, and as scientific and technological advances reshape how decisions are made across the development continuum, the role of DMPK will continue to evolve alongside the science it supports. For WuXi AppTec DMPK, the past 20 years have been defined not by a single breakthrough but by sustained collaboration, adaptability, and a commitment to enabling partners at every stage of discovery and development. The next chapter will likely demand even greater integration and innovation. The underlying goal, however, remains unchanged: to help bring better medicines to patients more efficiently and with greater confidence, in pursuit of a shared vision that “every drug can be made, and every disease can be treated.”

参考资料：

[1] Waring et al., (2015). An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat Rev Drug Discov, https://doi.org/10.1038/nrd4609

[2] Dowden and Munro, (2019). Trends in clinical success rates and therapeutic focus. Nat Rev Drug Discov, https://doi.org/10.1038/d41573-019-00074-z

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