ADC Pharmacokinetics Characterization

As a leader in antibody-drug conjugate (ADC) development, specialized teams in Creative Biolabs are experienced in characterizing ADC pharmacokinetics and we provide high-quality services and various assay formats for different analytes of an ADC.

Pharmacokinetics (PK) studies provide critical information regarding the behavior of a drug in circulation and its ultimate form after extensive in vivo metabolism. Results from PK studies often serve as guidelines for clinical trials designs, especially in the development of an antibody-drug conjugate (ADC). Due to the heterogeneous nature of ADCs, multiple analytes have to be assessed to reveal the ADC PK characteristics, making these studies more complex.

Parameters in ADC Pharmacokinetics Characterization

Creative Biolabs provides various formats of quantification assays to determine the in vivo pharmacokinetics profiles of an ADC. Several key parameters are determined by analyzing plasma/serum samples collected from animal experiments: total and conjugated antibodies, free and conjugated drugs, as well as catabolites.

  • Total and conjugated antibodies-- Creative Biolabs provides modified ELISA assays for total and conjugated antibody detection: (1) for total antibody quantification, the capturing reagent, depending on the availability of purified antigen, can be either the targeted antigen or a form of anti-human mAb. After total antibody capture, the amount is quantified using anti-human mAb HRP or biotin 2nd antibody; (2) conjugated antibody is captured by anti-drug antibody and detected/quantified with anti-CDR mAb.
  • Free and conjugated drugs, catabolites-- Creative Biolabs provides advanced LC-MS analysis approaches to assay for conjugated drug, free drug, and catabolites: (1) conjugated drug can be measured by affinity capture LC-MS/MS, a method that works for ADCs with chemically or enzymatically cleavable linkers. An ADC is isolated by affinity agents such as protein A and the conjugated drug is released by linker digestion and protein precipitate, and subsequently quantified using LC-MS/MS; (2) for free drug and catabolites quantification, ELISA competition assay or highly sensitive LC-MS analysis following extraction and precipitation of protein content are both available from Creative Biolabs.

ADC Pharmacokinetics Characterization Assays for the assessment of different ADC analytes. Top left: all antibodies, including unconjugated and conjugated versions, are quantified by using capture agent anit-CDR or anti-human mAb and detection reagents such as antibody with HRP or biotin. Top right: drug-conjugated antibodies are identified with anti-drug antibody and detected by biotin antigen or anti-CDR mAb. Bottom: contrary to drug-conjugated-antibody ELISA, antibody-conjugated drugs are captured by antigen and detected by anti-drug antibody.

Pharmacokinetics of ADCs

The pharmacokinetics of an ADC shares many typical characteristics with the unconjugated antibody, such as long half-life, low clearance, low volume of distribution, and poor oral bioavailability. However, after conjugating with small molecular drugs, an ADC acquires increased heterogeneity, resulting in the uniqueness of its PK profiles. With a full understanding of the complexity of ADC PK studies, Creative Biolabs provides both standard and customized PK analysis services for ADC development. Some of our featured services include:

(1)DAR Characterization-- It is of crucial importance for an ADC to remain stable during circulation before the payloads are effectively delivered to target sites to reduce adverse effects. However, in reality, plasma degradation or de-conjugation of an ADC might cause changes in the drug to antibody ratio (DAR), affecting the efficacy and safety of the ADC, as well as the bioanalytical methods. Creative Biolabs offers services to design and validate bioanalytical strategies and perform in vivo structural characterization of an ADC using methods such as ELISA and affinity capture LC-MS/MS.

(2)ADC Tissue Distribution-- Creative Biolabs provides both in vivo and ex vivo evaluation methods for ADC tissue distribution. These methods use radioactive compounds such as 125I or 111In and label ADCs via chemical conjugation. The Radioactive version of ADCs are applied to animals (usually mice) by intravenous injection. Our specialized team is highly experienced in conducting both PET imaging and postmortem radioactivity analysis to determine ADC tissue distribution.

(3)ADC Metabolism and Clearance-- Clinical researches have shown that ADCs exhibit similar catabolism and elimination process as the unconjugated monoclonal antibody. The catabolism of the ADCs is mediated by endocytosis or pinocytosis and they are eliminated from the system by enzymatic or chemical degradation in tissues such as kidney, lymph node, liver, spleen, and gut. Experts at Creative Biolabs offer postmortem analysis in combination with LC-MS/MS-based assays to determine the ADC metabolite and catabolite presented in various tissues. Moreover, Creative Biolabs also assists clients to discover in vivo elimination pathway of an ADC with radiolabeled technique. Major method involved is administrating animals with radiolabeled ADCs and measure the radioactivity in collected animal excreta such as feces, urine and bile.

For more detailed information, please contact our customer service or review our case studies for ADC pharmacokinetics evaluation.



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