A Multicentre Study Investigating The Pharmacokinetics And Pharmacodynamics Of Busulphan When Combined With Melphalan As Conditioning In Adult Autologous Transplant Recipients

Busulfan (Bu) is an alkylating agent commonly used in conditioning regimens prior to allogeneic stem cell transplantation (SCT). Whilst systemic drug exposure is thought to be critical for efficacy and safety of this agent (Kletzel et al. 2006; Bartelink et al. 2009; Andersson et al. 2002), there is a paucity of pharmacokinetic (PK) and pharmacodynamic (PD) evidence-based guidelines outlining how best to balance these potentially competing outcomes. In this study Bu PK was investigated in the setting of IV Bu-melphalan (mel) autologous SCT, with the primary intention of establishing factors influencing Bu exposure and how effectively PK assessment can be used to achieve desirable drug exposure. PD analysis was also performed to establish the effect of drug exposure on transplant-related toxicity.