ArticleClinical pharmacokinetics2014
Modelling the sitagliptin effect on dipeptidyl peptidase-4 activity in adults with haematological malignancies after umbilical cord blood haematopoietic cell transplantation.
Article in Clinical pharmacokinetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease.The New England journal of medicine · 2021Trial
- Fate of Hematopoiesis During Aging. What Do We Really Know, and What are its Implications?Stem cell reviews and reports · 2020Review
- An expanded role for dipeptidyl peptidase 4 in cell regulation.Current opinion in hematology · 2020Review
- Regimen-dependent synergism and antagonism of treprostinil and vildagliptin in hematopoietic cell transplantation.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Cord blood research, banking, and transplantation: achievements, challenges, and perspectives.Bone marrow transplantation · 2020Review
- Quickly attainable and highly engrafting hematopoietic stem cells.Blood science (Baltimore, Md.) · 2019Article
- Past, present, and future efforts to enhance the efficacy of cord blood hematopoietic cell transplantation.F1000Research · 2019Review
- High-dose sitagliptin for systemic inhibition of dipeptidylpeptidase-4 to enhance engraftment of single cord umbilical cord blood transplantation.Oncotarget · 2017Article
- Engineering cord blood to improve engraftment after cord blood transplant.Stem cell investigation · 2017Review
- Enhancing the efficacy of engraftment of cord blood for hematopoietic cell transplantation.Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis · 2016Review
- CD26/dipeptidylpeptidase IV-chemokine interactions: double-edged regulation of inflammation and tumor biology.Journal of leukocyte biology · 2016Review
- Modulation of Hematopoietic Chemokine Effects In Vitro and In Vivo by DPP-4/CD26.Stem cells and development · 2016Article
- Regulation of Chemokine Activity - A Focus on the Role of Dipeptidyl Peptidase IV/CD26.Frontiers in immunology · 2016Review
- Population Pharmacokinetic/Pharmacodynamic Modelling of Dipeptidyl Peptidase IV Inhibitors.Clinical pharmacokinetics · 2015Article
- Influence of a dual-injection regimen, plerixafor and CXCR4 on in utero hematopoietic stem cell transplantation and engraftment with use of the sheep model.Cytotherapy · 2014Article
- Inhibition of DPP4/CD26 and dmPGE₂ treatment enhances engraftment of mouse bone marrow hematopoietic stem cells.Blood cells, molecules & diseasesArticle
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
objectivesDipeptidyl peptidase-4 (DPP4) inhibition is a potential strategy to increase the engraftment rate of haematopoietic stem/progenitor cells. A recent clinical trial using sitagliptin, a DPP4 inhibitor approved for type 2 diabetes mellitus, has been shown to be a promising approach in adults with haematological malignancies after umbilical cord blood (UCB) haematopoietic cell transplantation (HCT). On the basis of data from this clinical trial, a semi-mechanistic model was developed to simultaneously describe DPP4 activity after multiple doses of sitagliptin in subjects with haematological malignancies after a single-unit UCB HCT.
methodsThe clinical study included 24 patients who received myeloablative conditioning followed by oral sitagliptin with single-unit UCB HCT. Using a nonlinear mixed-effects approach, a semi-mechanistic pharmacokinetic-pharmacodynamic model was developed to describe DPP4 activity from these trial data, using NONMEM version 7.2 software. The model was used to drive Monte Carlo simulations to probe the various dosage schedules and the attendant DPP4 response.
resultsThe disposition of sitagliptin in plasma was best described by a two-compartment model. The relationship between sitagliptin concentrations and DPP4 activity was best described by an indirect response model with a negative feedback loop. Simulations showed that twice daily or three times daily dosage schedules were superior to a once daily schedule for maximal DPP4 inhibition at the lowest sitagliptin exposure.
conclusionThis study provides the first pharmacokinetic-pharmacodynamic model of sitagliptin in the context of HCT, and provides a valuable tool for exploration of optimal dosing regimens, which are critical for improving the time to engraftment in patients after UCB HCT.
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Registered trials
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