Effect of Serum Parathyroid Hormone on Tacrolimus Therapy in Kidney Transplant Patients: A Possible Biomarker for a Tacrolimus Dosage Schedule

iPTH is not a significant factor influencing the tacrolimus C/D ratio

“… 2 In a rat model, secondary hyperparathyroidism (SHPT) decreased CYP3A activity, whereas SHPT therapy with cinacalcet restored it. 3 Consistent with this finding, but in contrast to Suzuki et al, 4 a positive correlation between iPTH level and TAC concentration was found in the present study by Tanaka et al 1 and also a study by Hirata et al 5 …”

Association of CYP3A5 polymorphisms and parathyroid hormone with blood level of tacrolimus in patients with end‐stage renal disease

“…The median iPTH level was 166.5 pg/ml, and the levels varied from 76.5 to 243.8 pg/ml (interquartile range). Table S1 shows tacrolimus C/D, CYP3A5 genotype, iPTH level, and co‐administered CYP3A inhibitors or inducer 15 in individual patients. Among the 48 patients, 19 received CYP3A inhibitors and one had CYP3A inducer.…”

“…In this study, a multiple logistic regression analysis by stepwise selection identified CYP3A5 polymorphism and serum iPTH level as significant factors associated with tacrolimus C/D (Table 2 ). In a previous report, Hirata et al 15 revealed that blood concentration of tacrolimus correlated significantly and positively with iPTH levels, but the association with CYP3A5 polymorphism was not evaluated. Furthermore, their report showed high tacrolimus concentrations even after transplantation, suggesting that iPTH‐induced inhibitory activity persisted.…”

“…Using primary rat hepatocytes and a human colon carcinoma cell line, secondary hyperparathyroidism (SHPT) model rats, Watanabe et al 14 showed that elevation of serum PTH caused a reduction in CYP3A expression in both the small intestine and liver, resulting in a significant reduction in CYP3A activity and a marked increase in the area under the curve (AUC) of midazolam, a typical substrate of CYP3A. Furthermore, Hirata et al 15 showed a significant positive correlation between the serum intact PTH (iPTH) level and blood tacrolimus concentration in 12 patients who underwent kidney transplantations who were not receiving potent CYP3A inhibitors. However, this previous report has not investigated the genotype of CYP3A5 polymorphism, a pivotal factor affecting the blood concentration of tacrolimus.…”

Response to “iPTH is not a significant factor influencing the tacrolimus C/D ratio”

“…However, this letter does not seem to rule out the influence of concomitant drugs, such as CYP3A inhibitors and inducers. According to the report by Hirata et al, 2 the positive correlation of iPTH level with TAC C/D was confirmed by excluding patients who received these concomitant drugs. In addition, our previous study found that the correlation coefficient of both factors increased from r = 0.305 to 0.428 by excluding these patients.…”