Altered Busulphan Exposure Associated with Concomitant Omeprazole during Hematopoietic Stem Cell Transplantation...

Area of Science:

• Pharmacology
• Oncology
• Drug Metabolism

Background:

• Busulphan is metabolized via cytochrome P450 enzymes, including CYP2C19.
• Omeprazole is a known inhibitor of CYP2C19.
• Altered busulphan metabolism can lead to significant toxicity due to its narrow therapeutic index.

Purpose of the Study:

• To investigate a potential drug-drug interaction between omeprazole and busulphan.
• To report clinical observations of busulphan exposure in patients receiving concomitant omeprazole.

Main Methods:

• Case report of two adult acute myeloid leukemia patients undergoing hematopoietic stem cell transplantation.
• Patients received oral busulphan (2 mg/kg b.i.d.) with fludarabine conditioning.
• Concomitant omeprazole treatment was administered to both patients.

Main Results:

• Unexpectedly elevated busulphan plasma area under the curve (AUC) values were observed.
• Dose reduction did not normalize exposure in one patient.
• Omeprazole discontinuation in the second patient led to a marked decrease in busulphan levels.

Conclusions:

• A potential drug-drug interaction between omeprazole and busulphan was observed.
• This interaction may be mediated by CYP-dependent metabolism inhibition.
• Concomitant omeprazole use during busulphan conditioning should be avoided; therapeutic drug monitoring is crucial.