医療薬学
Online ISSN : 1882-1499
Print ISSN : 1346-342X
ISSN-L : 1346-342X
総説
免疫抑制薬の TDM を基盤とした薬物治療管理のためのエビデンスの構築
内藤 隆文
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ジャーナル フリー

2011 年 37 巻 5 号 p. 277-287

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抄録

The immunosuppressive antimetabolites mycophenolate mofetil and mizoribine are widely used in combination with a calcineurin inhibitor for organ transplantation and autoimmune diseases. However, administering these antimetabolites at fixed doses often causes bone marrow toxicity or cytomegalovirus antigenemia. This review summarizes our findings from research in the clinical setting regarding evidence-based pharmaceutical care with antimetabolites in which therapeutic drug monitoring is used.
(1) The contribution of enterohepatic recirculation to the plasma disposition of mycophenolic acid (MPA) in lupus nephritis patients was similar to that in tacrolimus-treated kidney transplant recipients. MPA’s pharmacokinetics in lupus nephritis were characterized by higher clearance most likely due to better renal function.
(2) The renal clearance of MPA was higher in cyclosporine- than tacrolimus-treated kidney transplant recipients. The renal clearance ratio of MPA to creatinine was much higher than that for the unbound fraction of MPA. These pharmacokinetic data indicated the presence of renal tubular secretion in the urinary excretion process.
(3) Concomitant metal cations decreased the MPA concentration in tacrolimus- but not cyclosporine-treated kidney transplant recipients. This interaction may depend on the amount of biliary-excreted MPA glucuronide.
(4) The concentrative nucleoside transporter 1 (CNT1) genetic polymorphism G565A affected the bioavailability of mizoribine in kidney transplant recipients. CNT1 G565A may be a reason for inter-individual differences in the plasma disposition of mizoribine.
(5) The plasma disposition of MPA and its metabolites affected inosine 5’-monophosphate dehydrogenase activity in erythrocytes. 5’-monophosphate dehydrogenase activity might be a useful marker of long-term exposure to MPA.
The findings in this review should help achieve optimal dosing for antimetabolites through therapeutic drug monitoring in clinical practice.

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© 2011 日本医療薬学会
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