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Lansoprazole–Tacrolimus Interaction in Japanese Transplant Recipient with CYP2C19 Polymorphism

Pharmacist, Department of Pharmacy, Kyoto University Hospital; Faculty of Medicine, Kyoto University, Kyoto, Japan

Hideyuki Motohashi, PhD

Research Associate, Department of Pharmacy, Kyoto University Hospital; Faculty of Medicine, Kyoto University

Atsushi Yonezawa, BS

Department of Pharmacy, Kyoto University Hospital; Faculty of Medicine, Kyoto University

Masahiro Okuda, PhD

Associate Professor, Department of Pharmacy, Kyoto University Hospital; Faculty of Medicine, Kyoto University

Noriyuki Ito, MD

Lecturer, Pharmacist, Department of Urology, Graduate School of Medicine, Kyoto University

Shingo Yamamoto, MD

Associate Professor, Department of Urology, Graduate School of Medicine, Kyoto University

Osamu Ogawa, MD

Professor and Chairman, Department of Urology, Graduate School of Medicine, Kyoto University

Ken-ichi Inui, PhD

Professor and Director, Department of Pharmacy, Kyoto University Hospital; Faculty of Medicine, Kyoto University

Reprints: Ken-ichi Inui PhD, Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan, fax 81-75-751-4207, inui{at}kuhp.kyoto-u.ac.jp

OBJECTIVE: To report a patient with a high tacrolimus blood concentration after lansoprazole administration and assess the potential interaction between tacrolimus and lansoprazole.

CASE SUMMARY: A 34-year-old Japanese man underwent a living-donor kidney transplantation having received tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression. Lansoprazole was administered from postoperative day 4 as prophylaxis of ulcers. The trough concentration of tacrolimus increased markedly after the introduction of lansoprazole, while results of liver function tests were within normal limits. Lansoprazole was stopped on day 15 and was replaced with famotidine on day 17. The trough concentration of tacrolimus returned to the therapeutic range after administration of lansoprazole ceased. Genetic analysis revealed a heterozygous mutation at exon 5 of the CYP2C19 gene (CYP2C19^*1/^*2) in this patient.

DISCUSSION: Lansoprazole is metabolized by 2 enzymes, CYP2C19 and CYP3A4. Since tacrolimus is also metabolized by CYP3A4, the blood concentration of tacrolimus in this patient who had a CYP2C19 gene mutation may have been elevated by decreased hepatic elimination of lansoprazole. An objective causality assessment revealed that this interaction was probable.

CONCLUSIONS: Trough concentrations of tacrolimus should be monitored closely for optimizing the dosage regimen in patients receiving concomitant lansoprazole.

Key Words: CYP2C19, kidney transplantation, lansoprazole, tacrolimus

Published Online, March 9, 2004. www.theannals.com, DOI 10.1345/aph.1D366

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