Pulcolax (also known as FK506) is a novel macrolide immunosuppressant that has been widely used for immunosuppressive therapy after various organ transplants. Its narrow therapeutic window and very large inter-individual differences in pharmacokinetics require clinical testing of blood levels and dose adjustment based on the results of blood levels to achieve therapeutic goals while avoiding serious adverse effects. Achieving target therapeutic concentrations as soon as possible after kidney transplantation can reduce the incidence of early rejection and thus improve the long-term survival of the transplanted kidney. In clinical practice, it has been found that the blood concentrations of some patients taking the same oral dose of Pulcolax can vary greatly from one patient to another. Why do some patients who take the same dose of Pulcoloft orally have blood concentrations that do not reach standard concentrations (very low concentrations) and are prone to rejection? But some patients’ blood concentration exceeds the standard concentration (very high concentration) and are prone to a series of toxic side effects? At present, the clinical monitoring of blood concentration of Pulcolcolax is based on the pharmacokinetic characteristics of the patient at a single time point (morning fasting). The absorption, distribution, metabolism and excretion of plerocort and the genetic background of human genes related to the absorption and metabolism of plerocort are probably the main reasons for the inter-individual differences. 1. Absorption There is a very large inter-individual variation in the absorption process of Pulcolcitol after oral administration, and in general, its bioavailability is low, averaging about 25%, but can vary between 5 and 93%. Pulcoloft is rapidly absorbed, with peak concentrations generally reaching 0.5-1 hour after oral administration. In vivo studies have shown that the biotransformation in the intestine can vary up to 5-fold between individuals, and the proximal small intestine is the main site of first-pass metabolism of purocodone. Bile has no effect on the absorption of Pulcolocort. However, the absorption of purocoflor may be influenced by food, especially foods with high fat content, and in studies in healthy volunteers and liver transplant patients, it was found that eating reduced the absorption of purocoflor by 25-40% compared to fasting purocoflor, resulting in a 25-40% decrease in the area under the concentration curve (AUC). Therefore, it is emphasized to take the drug after empty or 2 hours after meal. 2.Distribution In the blood, pluricofol enters erythrocytes in large quantities, and the whole blood concentration is about 15 times higher than the plasma concentration (variation range 4-114 times), and the uptake of pluricofol by erythrocytes is non-linear. In plasma, placenta also binds mainly to various plasma protein components, including mainly α1 acidic glycoprotein, lipoprotein, globulin and albumin. The balance of plasma and erythrocyte distribution is influenced by erythrocyte pressure, placenta concentration, temperature and plasma proteins. Pulcolcitol can pass through the placenta and into breast milk, so its possible effects on the fetus should be considered for pregnant women, and women taking Pulcolcitol should stop breastfeeding. 3. Metabolism Pulcoloft is mainly metabolized by the CYP3A enzyme system in the liver and intestinal mucosa, and less than 0.5% of the drug in its original form is excreted in the urine and feces. The human CYP3A enzyme system includes four isoenzymes, CYP3A4, CYP3A5, CY3A7 and CYP3A43, and because these four enzymes have too many similarities in substrate selection, it is difficult to identify their respective roles in the metabolism of Pulcolax. In most adults, CYP3A4 is the predominant isoenzyme. Only some individuals express detectable CYP3A5 mRNA, and in these individuals, CYP3A5 accounts for 4-20% of the total CYP3A. expression of CYP3A4 has very large individual variation, reaching about 10-100 fold. CYP3A5 is heterogeneously expressed, and only individuals carrying at least one CYP3A5 *1 allele express CYP3A5 CYP3A5 is heterogeneously expressed, with only individuals carrying at least one CYP3A5 *1 allele expressing CYP3A5, but the expression of CYP3A5 in these individuals can account for 50% or more of the total CYP3A. Fifteen metabolites of Pulcoflor have been identified, most of which are inactive, and five of which are present in the blood. Clearance More than 95% of the metabolites of Pulcolax are excreted in the bile, and the average urinary excretion is only 2.4%. It has been reported that biliary obstruction can lead to accumulation of Pulcolizumab metabolites in the body. 5. Genetic background of drug metabolism The above phenomenon indicates that, in addition to many factors in the external environment, differences in the genetic background of genes related to the absorption and metabolism of Pulcolcolax between different individuals may affect the blood concentration and efficacy of the drug in patients. Pulcolcizumab is widely used in various organ transplants, and its narrow therapeutic window and large inter-individual variation in blood concentration have become a difficult problem for rational and effective drug administration in clinical practice. There have been many cases of acute rejection due to the difficulty in achieving the appropriate therapeutic concentrations in some patients with “standard” starting doses. Factors that may affect the absorption of Pulcoflor include the metabolism of the CYP3A enzyme system and the “anti-resorptive effect” of intestinal mucosal P-glycoprotein. Several studies have reported correlations between CYP3A5 gene polymorphisms and placenta concentrations in various post-transplant conditions of stable disease, and found that genotypes expressing CYP3A5 protein (*1 carriers) required larger doses to achieve the same concentrations than genotypes not expressing CYP3A5 (*3/*3 purets). Our results showed that patients with *3/*3 phenotypes had 2.2 to 4.3 times higher concentration/dose ratios of Pulcolovir than patients with *1/*1 and *1/*3 phenotypes. Some differences were also found in the concentration/dose ratio of purocoflor between *1/*1 and *1/*3 patients, although not as pronounced as between *1 carriers and *3/*3 pure congeners, but still showing statistical differences at 1 and 3 months postoperatively, i.e., among the 3 different CYP3A5 genotypes, *1/*1 patients had the lowest concentration/dose ratio and required the largest dose to reach the target concentration. The clinical significance of multidrug resistance gene polymorphism detection After transplantation, the dose should be adjusted as soon as possible to bring the blood concentration of Pulcolovir into the therapeutic range to reduce rejection or drug side effects. In our clinical practice, using a starting dose of 0.15 mg/kg/d and adjusting the dose according to the results of blood concentration measurement, the blood concentration of plerixofor in *1/*1 and *1/*3 patients was far below the target concentration (5.9ng/ml vs. 10ng/ml) at 1 week after transplantation, and only 23% of *1/*1 and *1/*3 patients had blood concentrations of 8ng/ml. Only 23% of *1/*1 and *1/*3 patients reached 8ng/ml, and most of the patients did not reach the target concentration and had a greater risk of acute rejection. In contrast, 20% of *3/*3 patients have blood levels higher than 20 ng/ml at 1 week postoperatively, and this group of patients is at a much higher risk for side effects such as central nervous system symptoms, post-transplant diabetes mellitus (PTDM), and nephrotoxicity. Clinicians can adjust the starting dose of Pulcoloft according to the characteristics of drug metabolism by different CYP3A5 genotypes to improve the efficacy of Pulcoloft and reduce its side effects. In particular, the relationship between blood concentration and CYP3A5 genotype at 7 days after surgery provides a direct basis for clinical selection of appropriate initial dose according to different CYP3A5 genotypes, and also lays the foundation for the monitoring of CYP3A5 gene polymorphism as a routine genetic background monitoring program for the selection of immunosuppressive treatment regimen. Therefore, in the transplantation clinic, immunosuppressants should be used rationally according to the effect of drug metabolism-related enzyme gene polymorphisms on blood concentration, thus making the clinical application of Pulcolax truly individualized. In order to determine the best drug and the most effective and safe dose for a certain patient at the beginning of treatment, this will have a good application prospect to guide the clinical rational use of drugs, improve the efficacy and reduce the adverse effects.