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Background <p>Busulphan is eliminated through glutathione conjugation, forming tetrahydrothiophene, which is subsequently oxidized to tetrahydrothiophene 1-oxide and sulfolane via cytochrome (CYP)-mediated pathways, including CYP2C19 and CYP3A4. Omeprazole is a known inhibitor of CYP2C19 and may interfere with the metabolism of busulphan metabolites, thereby altering systemic busulphan exposure. Given the narrow therapeutic index of busulphan, such interactions may have clinically significant consequences.</p> Case Presentation <p>We describe two adult patients who were diagnosed with acute myeloid leukemia and received oral busulphan (twice daily [b.i.d.]) at a dose of 2 mg/kg for two consecutive days (168 mg and 150 mg, respectively) as part of fludarabine/busulphan conditioning prior to hematopoietic stem cell transplantation. Both patients received concomitant treatment with omeprazole.</p> Results <p>Unexpectedly elevated busulphan plasma area under the curve (AUC) values were observed following the initial dose despite standard dosing (14.311 and 19.378 mg·h/L, respectively). Dose reduction in one patient did not normalize systemic exposure, whereas discontinuation of omeprazole in the second patient only was followed by a marked decrease in busulphan levels. On the second day, the corresponding AUC values were 19.320 (135%) and 13.772 mg·h/L (71%), respectively.</p> Conclusions <p>In these cases, a potential drug–drug interaction was observed between omeprazole and busulphan, possibly mediated through inhibition of CYP-dependent metabolism of busulphan metabolites. Concomitant use of omeprazole during busulphan conditioning should be avoided whenever possible. Therapeutic drug monitoring remains essential to optimize busulphan exposure and minimize the risk of treatment-related toxicity.</p>

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Altered Busulphan Exposure Associated with Concomitant Omeprazole during Hematopoietic Stem Cell Transplantation Conditioning: A Two-Case Report

  • 期刊论文

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  • 发表日期：

    2026年7月10日

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  • Ibrahim El-Serafi,
  • Rui He,
  • Ying Zhao,
  • Jonas Mattsson,
  • Moustapha Hassan

摘要

Background

Busulphan is eliminated through glutathione conjugation, forming tetrahydrothiophene, which is subsequently oxidized to tetrahydrothiophene 1-oxide and sulfolane via cytochrome (CYP)-mediated pathways, including CYP2C19 and CYP3A4. Omeprazole is a known inhibitor of CYP2C19 and may interfere with the metabolism of busulphan metabolites, thereby altering systemic busulphan exposure. Given the narrow therapeutic index of busulphan, such interactions may have clinically significant consequences.

Case Presentation

We describe two adult patients who were diagnosed with acute myeloid leukemia and received oral busulphan (twice daily [b.i.d.]) at a dose of 2 mg/kg for two consecutive days (168 mg and 150 mg, respectively) as part of fludarabine/busulphan conditioning prior to hematopoietic stem cell transplantation. Both patients received concomitant treatment with omeprazole.

Results

Unexpectedly elevated busulphan plasma area under the curve (AUC) values were observed following the initial dose despite standard dosing (14.311 and 19.378 mg·h/L, respectively). Dose reduction in one patient did not normalize systemic exposure, whereas discontinuation of omeprazole in the second patient only was followed by a marked decrease in busulphan levels. On the second day, the corresponding AUC values were 19.320 (135%) and 13.772 mg·h/L (71%), respectively.

Conclusions

In these cases, a potential drug–drug interaction was observed between omeprazole and busulphan, possibly mediated through inhibition of CYP-dependent metabolism of busulphan metabolites. Concomitant use of omeprazole during busulphan conditioning should be avoided whenever possible. Therapeutic drug monitoring remains essential to optimize busulphan exposure and minimize the risk of treatment-related toxicity.