FAQ – Analysis of Challenges and Solutions for Target Organ Biopsy in PK Studies

By performing biopsies on target organs, researchers can gain in-depth insights into the metabolism and distribution characteristics of a drug within specific tissues or organs. This enables a more accurate evaluation of the drug’s efficacy and safety, thereby assisting in the optimization of drug design.  Different administration methods, such as local delivery and targeted delivery, can influence drug absorption, bioavailability, and the suitability of specific experiments.  In PK studies, special administration methods may increase drug concentration in the target tissue, enhance therapeutic effects, or reduce the incidence of adverse reactions.

Yufeng Meng, the Assistant Director of DMPK at Medicilon, provides insights on the techniques and applications of target organ biopsy in PK studies. This information aims to help reduce confusion and challenges in PK trials.

1. Are there any requirements for selecting liver lobes during the puncture process? If so, what are the differences?

Yufeng Meng: We usually choose the left lobe of the liver for a liver puncture because the middle and right lobes involve the gallbladder and important blood vessels.  Before performing a liver puncture, the primary consideration is ensuring that we have sufficient confidence and technical proficiency to successfully complete the procedure.  Therefore, we must avoid the gallbladder and major blood vessels, hence the left lobe of the liver is preferred as the puncture site.

DMPK Services

Our Preclinical Pharmacokinetics Department has many professional scientists with rich theoretical knowledge and experimental experience for experimental design, implementation, bioanalysis and data analysis. Our Pharmacokinetics Lab has passed the NMPA GLP certification. Following the guiding principles of ICH, NMPA and FDA . The lab offers in vivo and in vitro pharmacokinetic tests according to the needs of our clients and provides clients with complete sets of pharmacokinetic evaluation and optimization services. Our acclaimed quality data collection and efficient experiment can meet our clients’ needs from early drug discovery to new drug filing.

Click Here

2. Can the liver be biopsied multiple times within 24 hours?

Yufeng Meng: We do not recommend frequent liver biopsies. It is advisable to wait at least 7 days between two procedures.  Although the liver has regenerative capacity, each biopsy requires animal anesthesia. Performing multiple operations within 24 hours would increase the number of times the animal needs to be anesthetized.  Additionally, each biopsy causes a certain degree of injury to the animal.  Therefore, we generally recommend performing biopsies once a week or once every two weeks to minimize the impact on the animals.

3. If an animal experiences abdominal pain after a kidney biopsy, how should it be managed?

Yufeng Meng: If an issue arises in the animals, it is first recommended to comprehensively assess its severity.  In cases of mild pain, it is sufficient to maintain observation. If the pain intensifies, appropriate medication should be administered to alleviate discomfort, and vital signs and symptom changes should be closely monitored.  If symptoms remain severe, including a rise in temperature or bleeding, an infection or other complications may occur.  At this point, further examinations such as ultrasound or CT scans should be conducted to identify the root cause of the issue. Based on the findings, a treatment plan should be formulated, such as using cephalosporin antibiotics for infection control.

4. How to determine whether intrathecal injection is successful?

Yufeng Meng: It is recommended to first attempt using a C-arm machine in combination with iodixanol contrast agent. During the procedure, ensure smooth aspiration of cerebrospinal fluid.  If aspiration is not smooth, the needle may be slightly adjusted or reinserted. Ensure smooth aspiration of cerebrospinal fluid before slowly injecting the iodixanol contrast agent.  At this point, the fluid should be clearly observed as flowing linearly within the subarachnoid space under C-arm imaging.  

5. For cisterna magna administration, how can the correct administration site be determined?

Yufeng Meng: When administering to the cisterna magna, pay attention to the actual procedure. First, ensure the needle is inserted slowly. There should be a sense of the needle entering an empty space at a certain depth. If cerebrospinal fluid can be smoothly aspirated at this point, it usually indicates successful administration.  In addition, similar to the intrathecal injection mentioned earlier, real-time imaging with a C-arm machine can be used. The C-arm machine, which provides continuous imaging, helps assess the needle insertion process.

6. If multiple liver punctures are needed throughout the day to monitor drug concentrations, will it affect the liver's metabolic function?

Yufeng Meng: This depends on the actual circumstances, but personally, I believe it could potentially affect liver function.