Asparaginase pharmacokinetics and implications of therapeutic drug monitoring

Abstract

Asparaginase is widely used in chemotherapeutic regimens for the treatment of acute lymphoblastic leukemia (ALL) and has led to a substantial improvement in cure rates, especially in children. Optimal therapeutic effects depend on a complete and sustained depletion of serum asparagine. However, pronounced interpatient variability, differences in pharmacokinetic properties between asparaginases and the formation of asparaginase antibodies make it difficult to predict the degree of asparagine depletion that will result from a given dose of asparaginase. The pharmacological principles underlying asparaginase therapy in the treatment of ALL are summarized in this article. A better understanding of the many factors that influence asparaginase activity and subsequent asparagine depletion may allow physicians to tailor treatment to the individual, maximizing therapeutic effect and minimizing treatment-related toxicity. Therapeutic drug monitoring provides a means of assessing a patient's current depletion status and can be used to better evaluate the potential benefit of treatment adjustments.

Keywords: Asparaginase; acute lymphoblastic leukemia; hypersensitivity; pharmacokinetics; silent inactivation; therapeutic drug monitoring.

Figure 1.

Mechanism of action of asparaginase [1]. Adapted with permission from Muller and Boos, 1998 [1].