Sugimoto R () Ikegami K () Enoki Y () Imafuku T () Fujimura R () Bi J () Nishida K () Sakaguchi Y () Murata M () Maeda H () Hirata K () Jingami S () Ishima Y () Tanaka M () Matsushita K () Komaba H () Fukagawa M () Otagiri M () Maruyama T () Biochem Pharmacol., in press 2017 (29) doi: 10.1016/j.bcp.2017.08.016 Chronic 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. In SHPT rats, hepatic and intestinal CYP3A expression was suppressed, but the changes were recovered by the administration of the calcimimetic cinacalcet, a PTH suppressor. Under the same experimental conditions, a pharmacokinetic study using orally administered midazolam, a substrate for CYP3A, showed that the AUC was increased by 5 times in SHPT rats, but that was partially recovered by a cinacalcet treatment. This was directly tested in rat primary hepatocytes and intestinal Caco-2 cells where the expression of the CYP3A protein was down-
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