The development and application of cyclosporine A as a calcineurin inhibitor can be considered a landmark advance in the history of organ transplantation technology, and it is now the basis of most immunosuppressive regimens in organ transplantation, mainly for the prevention of rejection of various types of organ transplants, such as graft-versus-host rejection after bone marrow transplantation. The drug is also widely used in the treatment of inflammatory or autoimmune diseases such as nephrotic syndrome, Crohn's disease, psoriasis and focal segmental glomerulosclerosis.

However, cyclosporine A has relatively severe hepatotoxicity and nephrotoxicity, and its pharmacokinetics are affected by a number of factors, including age, gender, body weight, time to transplantation of the patient, and drug-drug interactions, etc. Particularly important is the fact that its therapeutic window is very narrow, which makes the TDM of this drug particularly important.

Currently, the trough concentration (C0) of cyclosporine A is usually used as a drug concentration monitoring point in clinical practice, but long-term practical application has revealed that this strategy is not a good predictor of possible adverse reactions in patients. So is it possible that a better prediction can be obtained by using the AUC approach relative to C0? This study compared the two approaches inadult allogeneic stem cell recipients.

The trial used single-center random assignment to divide eligible subjects (18-65 years old) into AUC and C0 groups. Subjects received a standard treatment regimen and were tested for blood levels using finger blood during treatment. Trough concentrations were usually measured on days 0, 3, and 7 after initiation of the drug, and then weekly. The target value for the trough concentration was 250 μg/L. The AUC assay was performed using blood samples at 0, 2, and 3 hours after dosing, with a target value of 6,400 μg·h/L. Of the 40 subjects whose data were introduced, valid AUC data were completed and obtained in 15 cases, and valid C0 data were obtained in 13 cases.

After collecting information on subjects' gender, age, disease characteristics, and grading evaluation of toxic effects, it was found that all subjects had different levels of toxic side effects of the drug. In the AUC group, 60% of the subjects had grade 2/3 toxicities, while 46% of the subjects in the C0 group had the same level of toxicities. grade 4-5 toxicities did not occur in any of the subjects in either group. There was no significant difference between the two groups in the analysis of toxic side effects such as vomiting sensation, renal failure, and hypomagnesemia in subjects who used cyclosporine for 2-4 weeks. However, subjects were able to achieve target therapeutic blood levels earlier, as guided by the AUC assay values, relative to the C0 group. Moreover, comparing the data at any time stage showed that the number of subjects reaching the target was higher in the AUC group than in the C0 group, and there was a significant difference between the two groups.

From the above results, it can be seen that the strategy of using AUC did not effectively reduce the probability of the occurrence of drug toxicities associated with cyclosporine or the severity of toxicities relative to the C0 method of drug concentration monitoring, but it was able to control the effective drug concentration in patients more rapidly. Since this study only collected short-term data, further research is needed to determine whether the AUC strategy is useful for the control of toxic side effects in long-term treatment.