Clinical consequences of analytical variance and calculation strategy in oral busulfan pharmacokinetics

Matthew T. Olson, Lindsey Lombardi, William Clarke

Research output: Contribution to journalArticle

Abstract

Background: Busulfan pharmacokinetic (PK) monitoring of the area under the concentration-time curve (AUC) is necessary to minimize adverse events associated with both under- and over-dosing of busulfan during hematopoietic stem cell transplantation (HSCT). Three strategies are frequently used to calculate the AUC including in-house polynomial methods, the trapezoidal method (also called noncompartmental analysis), and the single compartment model with first-order elimination method. We compared these 3 methods, their clinical performance, and the relationship of AUC variance to analytical variance when each of these methods is used. Methods: Clinical busulfan PK data was reviewed from 159 patients receiving the first dose of oral busulfan while undergoing HSCT. These data were used as templates to simulate AUC results and actions with varying amounts of analytical precision. Results: Based on a predefined goal therapeutic target, the method for calculating AUC significantly changed the number of recommended busulfan dose adjustments (p

Original languageEnglish (US)
Pages (from-to)2316-2321
Number of pages6
JournalClinica Chimica Acta
Volume412
Issue number23-24
DOIs
StatePublished - Nov 20 2011

Fingerprint

Busulfan
Pharmacokinetics
Stem cells
Hematopoietic Stem Cell Transplantation
Polynomials
Monitoring

Keywords

  • Analytical variance
  • Busulfan
  • Clinical pharmacokinetics
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Clinical consequences of analytical variance and calculation strategy in oral busulfan pharmacokinetics. / Olson, Matthew T.; Lombardi, Lindsey; Clarke, William.

In: Clinica Chimica Acta, Vol. 412, No. 23-24, 20.11.2011, p. 2316-2321.

Research output: Contribution to journalArticle

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