Journal
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
Volume 93, Issue 3, Pages 283-291Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cmpb.2008.10.011
Keywords
Myelosuppression; Dose adaptation; Adaptive control; Bayesian forecasting; Pharmacodynamics; Neutropenia
Categories
Funding
- Swedish Cancer [15] Society
- Knut and Alice Wallenberg foundation
- Swedish Pharmaceutical Association
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Chemotherapy dosing in anticancer treatment is a balancing act between achieving concentrations that are effective towards the malignancy and that result in acceptable side-effects. Neutropenia is one major side-effect of many antitumor agents, and is related to an increased risk of infection. A model capable of describing the time-course of myelosuppression from administered drug could be used in individual dose selection. in this paper we describe the transfer of a previously developed semi-mechanistic model for myelosuppression. from NONMEM to a dosing tool in MS Excel, with etoposide as an example. The tool proved capable to solve a differential equation system describing the pharmacokinetics and pharmacodynamics, with estimation performance comparable to NONMEM. In the dosing tool the user provides neutrophil measures from a previous treatment course and request for the dose that results in a desired nadir in the upcoming course through a Bayesian estimation procedure. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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