The mechanism responsible for the decreased extra-renal CYP3A activity in chronic kidney disease (CKD) patients remains unknown. Using an animal model, we previously found that elevated levels of serum intact parathyroid hormone (iPTH) caused a reduced CYP3A activity. This retrospective observational study assessed the relationship between serum iPTH levels and the blood concentration or dosage of tacrolimus, a CYP3A substrate, after oral administration in kidney transplant patients.
View Article and Find Full Text PDFChronic kidney disease (CKD), which affects, not only renal clearance, but also non-renal clearance, is accompanied by a decline in renal function. Although it has been suggested that humoral factors, such as uremic toxins that accumulate in the body under CKD conditions, could be involved in the changes associated with non-renal drug clearance, the overall process is not completely understood. In this study, we report on the role of parathyroid hormone (PTH), a middle molecule uremic toxin, on the expression of drug metabolizing or transporting proteins using rats with secondary hyperparathyroidism (SHPT) as models.
View Article and Find Full Text PDFBackground: Susceptibility to cisplatin (CDDP) nephrotoxicity is known to vary between individuals, but the basis of this variation has not been fully elucidated. In the kidney, CDDP is taken up into the renal proximal tubular cells mainly via SLC22A2 organic cation transporter 2 (OCT2) and secreted into lumen via other transporters including SLC47A1 multidrug and toxin extrusion 1 (MATE1). Here, we explore the effect of single-nucleotide polymorphisms (SNPs) at 808G>T in OCT2 and at rs2289669 G>A in MATE1 on CDDP-induced adverse events.
View Article and Find Full Text PDFAlthough gemcitabine is frequently used in the treatment of cancer, it is associated with myelosuppression. An animal study showed that the tolerability of gemcitabine varied with changes in treatment time; however, no clinical data have verified this finding. The purpose of this study was to determine the relationship between treatment time and development of hematologic toxicity in patients treated with gemcitabine.
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