Abstract

Objective: Mycophenolic acid (MPA) exposure is associated with clinical outcomes in hematopoietic cell transplant (HCT) recipients. Various drug interaction studies, predominantly in healthy volunteers or solid organ transplant recipients, have identified medications which impact MPA pharmacokinetics. Recipients of nonmyeloablative HCT, however, have an increased burden of comorbidities, potentially increasing the number of concomitant medications and potential drug interactions (PDI) affecting MPA exposure. Thus, we sought to be the first to characterize these PDI in nonmyeloablative HCT recipients. Materials and methods: We compiled PDI affecting MPA pharmacokinetics and characterized the prevalence of PDI in nonmyeloablative HCT recipients. A comprehensive literature evaluation of four databases and PubMed was conducted to identify medications with PDI affecting MPA pharmacokinetics. Subsequently, a retrospective medication review was conducted to characterize the cumulative PDI burden, defined as the number of PDI for an individual patient over the first 21 days after allogeneic graft infusion, in 84 nonmyeloablative HCT recipients. Results: Of the 187 concomitant medications, 11 (5.9%) had a PDI affecting MPA pharmacokinetics. 87% of 84 patients had one PDI, with a median cumulative PDI burden of 2 (range 0 – 4). The most common PDI, in descending order, were cyclosporine, omeprazole and pantoprazole. Conclusion: Only a minority of medications (5.9%) have a PDI affecting MPA pharmacokinetics. However, the majority of nonmyeloablative HCT recipients had a PDI, with cyclosporine and the proton pump inhibitors being the most common. A better understanding of PDI and their management should lead to safer medication regimens for nonmyeloablative HCT recipients.

Highlights

  • Nonmyeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation (HCT) have expanded the availability of this procedure to patients who cannot tolerate the toxicity of high-dose conditioning due to age or comorbidity [1]

  • An evaluation of potential drug interactions (PDI) in nonmyeloablative HCT patients is imperative, especially considering the increased attention given to drug interactions in cancer patients receiving standard dose chemotherapy [2] and in solid organ transplant recipients [3]

  • We evaluated concomitant medications in a cohort of nonmyeloablative HCT recipients who participated in a prospective biomarker study between November 2008 and February 2012

Read more

Summary

Introduction

Nonmyeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation (HCT) have expanded the availability of this procedure to patients who cannot tolerate the toxicity of high-dose conditioning due to age or comorbidity [1]. 75% of nonmyeloablative HCT recipients have pre-transplant comorbidities, as defined by the HCT-comorbidity index (HCT-CI), possibly increasing the number of potential drug interactions (PDI) [1]. An evaluation of PDI in nonmyeloablative HCT patients is imperative, especially considering the increased attention given to drug interactions in cancer patients receiving standard dose chemotherapy [2] and in solid organ transplant recipients [3]. Mycophenolate mofetil (MMF), an ester prodrug, is a key component of postgrafting immunosuppression after nonmyeloablative HCT. MMF is rapidly hydrolyzed to mycophenolic acid (MPA), its therapeutically active metabolite, by esterases in the gastrointestinal (GI) tract. Metabolites, of which MPA-7-O-glucuronide predominates, are excreted renally or into the bile via the ATP binding cassette transporter 2 (ABCC2, multidrug resistanceassociated protein 2 or MRP2) [4]. The subsequent reabsorption of MPA as part of enterohepatic recycling (EHC)

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call