Pharmacokinetics of high-dose chemotherapy

There is considerable variation in the severity of preparative regimen-related toxicity (RRT) in hematopoietic stem-cell transplantation (HSCT). This variation has been recognized to be due, in part, to the wide variation in the pharmacokinetics (PK) of high-dose chemotherapy (HDC). Consequently, therapeutic drug modeling and pharmacokinetic-directed therapy (PKDT) represents an attractive strategy in this setting. Advances in our understanding of drug metabolism, the nature of the active metabolites, and the ability to measure drug concentrations have led to the point where for some agents it is now possible to treat to a given PK end point with a great deal of reliability. In-depth knowledge of the PK and pharmacodynamics (PD) associations of the agents employed in the high-dose setting will make possible more efficient research into preparative regimen dosing intensity and comparisons of different preparative regimens as well as safer HSCT overall. In this review, we discuss PK and PD studies of high-dose cyclosphamide, melphalan, thiotepa, carmustine, cisplatin, carboplatin, paclitaxel, docetaxel, and busulfan.