The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation

SUMMARY: Busulfan (Bu) is an important component of some myeloablative regimens prior to stem cell transplantation (SCT). Over the last few years it has been shown that other drugs

administered concomitantly can influence Bu pharmacokinetics. In the present study, we compared Bu concentrations (trough levels) in three groups of patients. Group A (_n_=5) received

metronidazole as graft-versus-host disease prophylaxis during Bu treatment. Group B (_n_=9) received Bu only for 2 days followed by 2 days of Bu and metronidazole. Group C (_n_=10) was a

control group that received Bu without metronidazole. The mean Bu levels for Group A receiving metronidazole during conditioning was significantly (_P_<0.001) higher (948±280 ng/ml),

compared to those observed in the control group (507±75 ng/ml). In Group B, the administration of metronidazole resulted in a significant (_P_<0.001) increase in Bu levels (807±90 ng/ml)

during the last 2 days, compared to 452±68 ng/ml during the first 2 days. In Group A, one patient died with multiorgan failure, three experienced veno-occlusive disease (VOD) and one

developed hemorrhagic cystitis. Elevated liver transaminases (AST, ALT) and bilirubin were detected in all Group A patients. In Group B, six patients had elevated liver function tests but no

VOD was observed. We conclude that metronidazole should not be administered simultaneously with Bu to avoid the high plasma levels of Bu, which may lead to severe toxicity and/or treatment

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Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS IMPACT OF BUSULFAN PHARMACOKINETICS ON OUTCOME IN ADULT PATIENTS RECEIVING AN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION

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their gratitude to the Swedish Children Cancer Society (BCF) grant no. PROJ 01/059, King Gustav V Jubilee fund grant no. 00:510 and Stockholms Cancer Foundation grant no. 02:119. AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Division of Hematology, Department of Medicine, Laboratory of Hematology, Huddinge University Hospital, Stockholm, Sweden C Nilsson, P Ljungman & M

Hassan * Center for Allogeneic Stem Cell Transplantation, Huddinge University Hospital, Stockholm, Sweden J Aschan, P Hentschke & O Ringdén Authors * C Nilsson View author publications

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PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nilsson, C., Aschan, J., Hentschke, P. _et al._ The effect of metronidazole on busulfan pharmacokinetics in patients

undergoing hematopoietic stem cell transplantation. _Bone Marrow Transplant_ 31, 429–435 (2003). https://doi.org/10.1038/sj.bmt.1703896 Download citation * Received: 14 March 2002 *

Accepted: 20 October 2002 * Published: 28 March 2003 * Issue Date: 01 March 2003 * DOI: https://doi.org/10.1038/sj.bmt.1703896 SHARE THIS ARTICLE Anyone you share the following link with

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content-sharing initiative KEYWORDS * busulfan * pharmacokinetics * metronidazole * SCT * toxicity * drug interaction