sirolimus需要注意的事项有什么？

Compared with standard-dose calcineurin inhibitors, sirolimus has almost no nephrotoxicity and has unique immunological advantages in inducing tolerance and can improve renal transplant function. At present, this drug has been widely used in the treatment of kidney transplant patients. In order for patients to benefit from it, patients need to pay high attention to the following matters:

(1) For the pediatric population, since the safety and efficacy of this drug in pediatric patients under 13 years of age have not yet been determined, blood trough concentration monitoring should be performed when pediatric patients under 13 years of age use this drug.

(2) For elderly patients, in the clinical trials of sirolimus, there were not enough cases of patients aged 65 and above to determine whether the safety and efficacy of the drug in this group are different from that of younger patients. Data on sirolimus trough concentrations suggest that age-based dose adjustment is not required in elderly patients with renal disease.

(3) For pregnant and lactating women, sirolimus needs to be contraindicated.

(4) Sirolimus (i.e., sirolimus) is known to be a substrate of cytochrome CYP3A4 and P-glycoprotein. When sirolimus is taken simultaneously with some drugs, its pharmacokinetic interaction is as follows: Sirolimus is rapidly absorbed after taking oral solution, and the average peak time after a single oral dose is about 1 hour; in kidney transplant recipients, the average peak time after multiple oral doses is about 2 hours. High-fat meals can increase the absorption of sirolimus, so it is recommended that oral sirolimus tablets should be taken regularly with or without food. The average sirolimus volume of distribution (Vss/F) was 12±8 L/kg. Sirolimus is extensively bound to human plasma proteins (approximately 92%). Sirolimus is a substrate of cytochrome P450 III A (CYP3A) and P-glycoprotein (P-gp). Sirolimus is metabolized by CYP3A4 in the intestinal wall and liver, and can be reversed by P-gp from the intestinal epithelial cells into the intestinal lumen. Therefore, drugs acting on these two proteins may affect the absorption and clearance of sirolimus.