ArticleJournal of pharmacokinetics and pharmacodynamics2001
A mechanism-based pharmacokinetic model for the cytochrome P450 drug-drug interaction between cyclophosphamide and thioTEPA and the autoinduction of cyclophosphamide.
Article in Journal of pharmacokinetics and pharmacodynamics, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00851110 (A Prospective Randomized Feasibility and Phase II Adjuvant Breast Cancer Study of the Netherlands Working Party for Autotransplantation in Solid Tumors.), which is not on this map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
A Prospective Randomized Feasibility and Phase II Adjuvant Breast Cancer Study of the Netherlands Working Party for Autotransplantation in Solid Tumors.
Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Exposure-Toxicity Association of Cyclophosphamide and Its Metabolites in Infants and Young Children with Primary Brain Tumors: Implications for Dosing.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin's lymphoma.European journal of cancer (Oxford, England : 1990) · 2016Trial
- Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues.British journal of clinical pharmacology · 2007Trial
- High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy.British journal of cancer · 2006Trial
- A Novel Algorithm to Improve PrEP Adherence Monitoring Using Dried Blood Spots.Clinical pharmacology and therapeutics · 2023Article
- Overestimation of the effect of (fos)aprepitant on intravenous dexamethasone pharmacokinetics requires adaptation of the guidelines for children with chemotherapy-induced nausea and vomiting.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Article
- Population Pharmacokinetic, Pharmacogenetic, and Pharmacodynamic Analysis of Cyclophosphamide in Ethiopian Breast Cancer Patients.Frontiers in pharmacology · 2020Article
- Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia.Neonatology · 2019Article
- Deep learning improves prediction of drug-drug and drug-food interactions.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Population pharmacokinetics analysis of cyclophosphamide with genetic effects in patients undergoing hematopoietic stem cell transplantation.European journal of clinical pharmacology · 2013Article
- Covariate pharmacokinetic model building in oncology and its potential clinical relevance.The AAPS journal · 2012Review
- Characterization of the time course of carbamazepine deinduction by an enzyme turnover model.Clinical pharmacokinetics · 2009Article
- Population pharmacokinetics of cyclophosphamide and metabolites in children with neuroblastoma: a report from the Children's Oncology Group.Journal of clinical pharmacology · 2009Article
- Population pharmacokinetics and pharmacodynamics for treatment optimization in clinical oncology.Clinical pharmacokinetics · 2008Review
- Dealing with time-dependent pharmacokinetics during the early clinical development of a new leukotriene B4 synthesis inhibitor.Pharmaceutical research · 2006Article
- Population pharmacokinetics of lopinavir in combination with ritonavir in HIV-1-infected patients.British journal of clinical pharmacology · 2005Article
- Clinical pharmacokinetics of cyclophosphamide.Clinical pharmacokinetics · 2005Review
- Integrated Population Pharmacokinetic Model of both cyclophosphamide and thiotepa suggesting a mutual drug-drug interaction.Journal of pharmacokinetics and pharmacodynamics · 2004Article
- Pharmacokinetic-pharmacodynamic guided trial design in oncology.Investigational new drugs · 2003Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclophosphamide (CP) is widely used in high-dose chemotherapy regimens in combination with thioTEPA. CP is a prodrug and is activated by cytochrome P450 to 4-hydroxycyclophosphamide (HCP) which yields the final cytotoxic metabolite phosphoramide mustard (PM). The metabolism of CP into HCP exhibits autoinduction but is inhibited by thioTEPA. The aim of this study was to develop a population pharmacokinetic model for the bioactivation route of CP incorporating the phenomena of both autoinduction and the drug-drug interaction between CP and thioTEPA. Plasma samples were collected from 34 patients who received high-dose CP, thioTEPA and carboplatin in short infusions during 4 consecutive days. Elimination of CP was described by a noninducible route and an inducible route leading to HCP. The latter route was mediated by a hypothetical amount of enzyme. Autoinduction leads to a zero-order increase in amount of this enzyme during treatment. Inhibition by thioTEPA was modeled as a reversible, competitive, concentration-dependent inhibition. PM pharmacokinetics were described by first-order formation from HCP and first-order elimination. The final models for CP, HCP, and PM provided an adequate fit of the experimental data. The volume of distribution, noninducible and initial inducible clearances of CP were 31.0 L, 1.58 L/hr and 4.76 L/hr, respectively. The enzyme amount increased with a zero-order rate constant of 0.041 amount * hr-1. After each thioTEPA infusion, however, approximately 80% of the enzyme was inhibited. This inhibition was reversible with a half-life of 6.5 hr. The formation and elimination rate constants of PM were 1.58 and 0.338 hr-1, respectively. The developed model enabled the assessment of the complex pharmacokinetics of CP in combination with thio TEPA. This model provided an adequate description of enzyme induction and inhibition and can be used for treatment optimization in this combination.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.