ArticleCancer chemotherapy and pharmacology2015
Population pharmacokinetic/dynamic model of lymphosuppression after fludarabine administration.
Article in Cancer chemotherapy and pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Impact of fludarabine exposure on CAR T-cell outcomes in patients with large B-cell lymphoma.Blood advances · 2026Article
- Physiologically Based Pharmacokinetic Virtual Twin Approach for Fludarabine Dosing in Pediatric Hematopoietic Stem Cell Transplantation.CPT: pharmacometrics & systems pharmacology · 2026Article
- The presence of busulfan metabolites and pharmacometabolomics in plasma drawn immediately before allograft infusion in hematopoietic cell transplant recipients.Clinical and translational science · 2023Article
- Fludarabine exposure in the conditioning prior to allogeneic hematopoietic cell transplantation predicts outcomes.Blood advances · 2019Article
- Population Pharmacokinetics of Fludarabine in Children and Adults during Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation.Clinical pharmacokinetics · 2019Article
- Pharmacokinetics and Pharmacodynamics of Treosulfan in Patients With Thalassemia Major Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.Clinical pharmacology and therapeutics · 2018Article
- Population pharmacokinetics of fludarabine in patients with aplastic anemia and Fanconi anemia undergoing allogeneic hematopoietic stem cell transplantation.Bone marrow transplantation · 2017Article
- Genotypes Affecting the Pharmacokinetics of Anticancer Drugs.Clinical pharmacokinetics · 2017Review
- Association of fludarabine pharmacokinetic/dynamic biomarkers with donor chimerism in nonmyeloablative HCT recipients.Cancer chemotherapy and pharmacology · 2015Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
purposeQuantitative relationships between 9-β-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) concentrations and lymphosuppression have not been reported, but would be useful for regimen design. A population pharmacokinetic/pharmacodynamic model was constructed in this study using data from 41 hematopoietic cell transplant (HCT) recipients conditioned with busulfan in combination with fludarabine (total dose 120 mg/m², Protocol 1519) or with fludarabine (total dose 250 mg/m²) with rabbit antithymocyte globulin (rATG, Protocol 2041).
methodsIndividual pharmacokinetic parameters were fixed to post hoc Bayesian estimates, and circulating absolute lymphocyte counts (ALC) were obtained during the 3 weeks prior to graft infusion. A semi-physiological cell-kill model with three lymphocyte transit compartments was applied and aptly characterized the time course of suppression of circulating ALC by fludarabine administration. Drug- and system-specific parameters were estimated using a maximum likelihood expectation maximization algorithm, and the final model was qualified using an internal visual predictive check.
resultsThe final model successfully characterized the time course and variability in ALC. Pharmacodynamic parameters exhibited considerable between subject variability (38.9-211 %). The HCT protocol was the only covariate associated with the pharmacodynamic parameters, specifically the lymphocyte kill rate, the transit rate between lymphocyte compartments, and the baseline ALC.
conclusionsThis model can be used to simulate the degree of lymphosuppression for design of future fludarabine-based conditioning regimens.
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