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Busulfan AUC Dosing: Improved Busulfan Target AUC and Dosing Accuracy

Megan N. Freeland, PharmD
December 1, 2020

Busulfan dosing requires an accurate, reliable method of estimating the area under the curve (AUC). Clinicians also need to know the optimal busulfan AUC exposure range to aim for. 

While there are existing norms regarding target AUC for busulfan, newer research suggests that changes to the recommended exposure range may be in order. Additionally, a novel, technology-driven approach to busulfan dosing can help improve patient safety and outcomes. We’ll discuss both in this article.

Busulfan Dosing and Target Busulfan AUC

Busulfan is an integral component of pre-hematopoietic stem cell transplant (HCT) conditioning regimens. For HCT clinicians at your institution, managing busulfan therapy safely is necessary during this pre-HCT phase. They may reference hospital-specific or industry guidelines to identify a target busulfan AUC.

A historical busulfan AUC target of 900–1500 μM*min (59.1–98.5 mg*h/L) has been accepted for several years. The idea behind this goal range is that exposures above this range are more likely to cause dose-limiting toxicity, while exposure below the range may not be high enough to completely ablate bone marrow cells, leading to a risk of graft failure or relapse post-transplant. 

But pharmacologists from InsightRX, along with a team of independent pharmacologists and researchers from a variety of research institutions, have identified a busulfan AUC target that may be safer and more efficacious. 

Based on a multicenter retrospective cohort analysis, we believe patients may experience better clinical outcomes with a target busulfan exposure of 1223–1575 μM*min (78–101 mg*h/L). This higher target range tends to correlate with better outcomes and lesser risk for graft failure or relapse.

How to Calculate Busulfan AUC

When it comes to calculating busulfan AUC, clinicians need to be able to adopt consistent, standardized methods for estimating busulfan AUC since different estimation methodologies may produce different, inconsistent results. 

Two methods of calculating AUC are:

  1. Traditional noncompartmental analysis (NCA) 
  2. Novel population pharmacokinetic (PK)-based precision dosing, also called model-informed precision dosing (MIPD)

NCA uses a concentration-time graph to estimate AUC, but tends to underestimate exposure which can lead to higher doses of busulfan than necessary. MIPD is a more precise, individualized method of estimating busulfan AUC, which correlates to a more accurate busulfan dose.

Learn more about NCA vs. model-informed precision dosing for busulfan

How InsightRX makes AUC dosing easier, more precise, safer

For department leaders and other clinicians, shifting to a population PK AUC-based dosing approach may seem labor-intensive and somewhat intimidating, but platforms like InsightRX Nova make the entire process accessible and easy to implement. 

We use a process called Bayesian forecasting to inform our precision dosing PK models. Our Bayesian dosing software takes the individualized, patient-specific data you input and process it to produce highly-accurate busulfan dosing recommendations.

Interesting note: Busulfan isn’t the only medication our precision dosing software can be used for. Recent updates to vancomycin dosing and monitoring guidelines have placed it among the ranks of medications that are ideally dosed according to AUC. Institutions are able to use the InsightRX Nova platform to dose a variety of medications, including busulfan and vancomycin.

With MIPD, clinicians won’t need to lament over whether or not they perform a calculation correctly or whether their AUC estimation is too low or high. They can feel confident that the busulfan doses patients receive are optimized to their specific profile, giving them the best chance of HCT success.

To get a feel for how InsightRX would work for your institution, request a free trial.


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