Sirolimus, also known as rapamycin, is a macrolide immunosuppressant that was originally discovered from bacteria in the soil of Easter Island ^[1]. Its main clinical use is to prevent organ transplant rejection, particularly in kidney, liver and heart transplants ^[1]. Sirolimus is also used in the treatment of certain autoimmune diseases and as an adjuvant therapy for certain types of cancer. The mechanism of action of sirolimus is primarily by inhibiting the activity of the mammalian target of rapamycin (mTOR) protein, which interferes with cell cycle progression and inhibits cell proliferation and immune responses. This makes it very effective in controlling overactivity of the immune system^[2].

Clinical challenges with Sirolimus

As an important immunosuppressant, sirolimus plays a key role in organ transplantation and in the treatment of certain autoimmune diseases. However, its clinical application faces many challenges, including large individual differences, narrow therapeutic window, drug-drug interactions, management of adverse effects, patient compliance, financial burden, technical requirements for monitoring, dose-adjustment strategies, use in special populations, and assessment of long-term efficacy and safety [3]. These challenges require clinicians, pharmacists, and technicians to work closely together to ensure the therapeutic efficacy and safety of sirolimus while improving patients' quality of life through individualized treatment, accurate monitoring, and patient guidance.

Significance of sirolimus TDM 

By implementing therapeutic drug monitoring (TDM) of sirolimus, physicians are able to accurately assess the concentration of the drug in the patient's bloodstream, which is essential for optimizing treatment outcomes. As an immunosuppressant, sirolimus plays an important role in the treatment of organ transplantation and certain autoimmune diseases. However, due to its narrow therapeutic window, i.e. the small range of effective concentrations of the drug, concentrations that are too high or too low can compromise therapeutic efficacy or increase the risk of adverse effects. By monitoring blood concentrations, clinicians can adjust drug dosing based on patient-specific factors, such as metabolic rate and co-administration, to ensure that drug concentrations are maintained within the therapeutic window. In addition, TDM helps identify and resolve patient compliance issues in a timely manner, ensuring that patients receive consistent and stable treatment, thereby improving treatment success rates and patient quality of life.

Sirolimus, as a potent immunosuppressant, may trigger a series of adverse reactions during treatment, and the occurrence of these reactions is directly related to the blood levels in the patient's body. Through therapeutic drug monitoring (TDM), physicians are able to monitor sirolimus blood levels in real time, allowing for more precise dosage adjustments during treatment. This monitoring tool is crucial for preventing and minimizing adverse effects, and can effectively avoid serious problems such as bone marrow suppression, hyperlipidemia, and proteinuria caused by high drug levels. Through TDM, physicians are able to ensure drug efficacy while minimizing the risk of patients suffering adverse reactions and improving the safety of treatment. In addition, TDM can also help identify individual differences in patients in a timely manner, and customize the most appropriate treatment plan for each patient, thus improving the overall treatment effect and quality of life for patients.

Significant inter-patient variability in pharmacokinetics means that the absorption, distribution, metabolism, and excretion of sirolimus vary from individual to individual. These differences can be influenced by a variety of factors including genetic background, age, gender, body weight, liver and kidney function, and concomitant medications. With TDM, physicians are able to create a personalized treatment plan for each patient by adjusting the drug dose based on each patient's blood concentration data to ensure that the drug concentration is maintained within the therapeutic window. This approach not only improves treatment safety and reduces the risk of side effects, but also increases treatment efficacy and ensures that patients achieve optimal health benefits. The implementation of individualized treatment makes medical decision-making more scientific and rational, helping to improve patient satisfaction and treatment success.

TDM allows physicians to accurately adjust drug dosages based on a patient's sirolimus blood levels, thereby avoiding treatment failure or drug toxicity due to improper dosing. This precision medicine reduces the need for repeated dose adjustments and lowers the risk of hospitalization due to adverse drug reactions. By reducing unnecessary hospitalizations and emergency room visits, the healthcare system can allocate resources more efficiently to serve more patients. In addition, TDM helps reduce healthcare costs by reducing drug waste and additional healthcare costs associated with treatment failure. On a broader level, TDM improves the overall quality of healthcare services by improving treatment outcomes and patient satisfaction, thereby maximizing the use of healthcare services in the face of limited healthcare resources.

In conclusion, sirolimus TDM is a key tool for achieving precision medicine and improving patient outcomes and quality of life.