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A Significant Influence of Metronidazole on Busulfan Pharmacokinetics: A Case Report of Therapeutic Drug Monitoring

Chung, Hyewon, MD*; Yu, Kyung-Sang, MD, PhD*; Hong, Kyung, Taek, MD; Choi, Jung, Yoon, MD; Hong, Che, Ry, MD; Kang, Hyoung, Jin, MD, PhD; Park, Kyung, Duk, MD, PhD; Shin, Hee, Young, MD, PhD; Lee, SeungHwan, MD, PhD*

doi: 10.1097/FTD.0000000000000395
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Abstract: Busulfan is a cytotoxic agent used in preconditioning for hematopoietic stem cell transplantation. Therapeutic drug monitoring of busulfan is necessary owing to its narrow therapeutic range. Patients undergoing preconditioning are susceptible to infection and might require coadministration of antibiotics. We present a case study of a 3-year-old girl with precursor T-cell acute lymphoblastic leukemia who received intravenous busulfan before hematopoietic stem cell transplantation. Metronidazole was coadministered before the third dose of busulfan because of Clostridium difficile infection. The daily pharmacokinetic analysis revealed that the clearance reduced to 57% of that before the coadministration. Although the underlying mechanism is unclear, a significant pharmacokinetic interaction was observed between busulfan and metronidazole, underscoring the importance of therapeutic drug monitoring.

*Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital; and

Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Correspondence: Seung Hwan Lee, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Republic of Korea (e-mail:

The authors declare no conflict of interest.

Received November 26, 2016

Accepted January 31, 2017

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