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Xenobiotica
the fate of foreign compounds in biological systems
Volume 45, 2015 - Issue 12
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Pharmacogenetics

Effects of CYP3A5 polymorphism and the tacrolimus 12 h concentration on tacrolimus-induced acute renal dysfunction in patients with lupus nephritis

, , , , , , , , & show all
Pages 1147-1153 | Received 15 Mar 2015, Accepted 23 Apr 2015, Published online: 20 Jul 2015
 

Abstract

1. The purpose of the present study was to investigate the effect of tacrolimus concentration in blood 12 h after administration (C12h) on acute renal dysfunction in patients with lupus nephritis (LN) taking tacrolimus once daily.

2. Five of the 35 LN patients experienced tacrolimus-induced acute renal dysfunction.

3. The average annual C12h of tacrolimus was higher for patients with events of elevated serum creatinine level than for patients not experiencing these events [6.4 (5.6–8.8) versus 2.8 (2.2–4.6) ng/mL, respectively, p = 0.001].

4. The average annual tacrolimus C12h was higher for patients with CYP3A5*3/*3 (PM) than for patients with the CYP3A5*1 allele (EM) [4.6 (3.2–6.6) versus 2.5 (2.0–3.1) ng/mL, respectively, p = 0.002].

5. The area under the receiver operating characteristic was 0.887, which gave the best sensitivity (80.0%) and specificity (86.7%) at a tacrolimus C12h (average annual C12h or C12h at events) threshold of 5.2 ng/mL.

6. C12h measurements, CYP3A5 genotyping and dose adjustments of tacrolimus should be performed to prevent acute renal dysfunction in LN patients taking tacrolimus once daily.

Declaration of interest

This work was supported by a grant (No. 20722276) from the Japan Society for the Promotion of Science, Tokyo, Japan.

The authors declare no conflict of interest associated with this manuscript.

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