Study of Clinical Pharmacokinetics in Oncology Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics".

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 2068

Special Issue Editors

Department of Clinical and Experimental Medicine School of Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy
Interests: cancer cell biology; mechanisms of cancer cell death; cancer stem cells; drug resistance; tumor microenvironment; microbiome and cancer; pharmacology; pharmacokinetics of antineoplastic drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Anticancer drugs have different pharmacokinetic profiles depending on their chemical structures and on the schedules used in clinical practice. Furthermore, antineoplastic agents may significantly interact with drugs that are used to treat co-morbidities in oncological patients. Therefore, the pharmacokinetics of anticancer drugs should be adequately described and investigated by the scientific literature in order to avoid severe adverse drug reactions and to maintain plasma drug concentrations within the therapeutic range. It is worth noting that the alteration of pharmacokinetic parameters may determine a therapeutic failure and a pharmacokinetic-based resistance to the treatment, reducing the survival of cancer patients and worsening quality of life. Relationships between systemic exposure to anticancer drugs, for example, those described by the area under the concentration–time curve, and both toxicity and response have been described for various classes of drugs. However, the relationship between pharmacokinetic parameters and the response rate is usually neglected for many anticancer drugs, and this may be related to the lack of studies describing this particular but fundamental aspect of anticancer pharmacology. The scientific community should prioritize the active therapeutic drug monitoring of anticancer drugs in order to rationalize the administration of these compounds. This is even more urgent in the paediatric field.

With this Special Issue, we hope to encourage submissions that discuss the current state-of-the-art, address ongoing knowledge gaps, and focus on ongoing controversies related to clinical pharmacokinetics in oncology diseases. 

Prof. Dr. Guido Bocci
Prof. Dr. Antonello Di Paolo
Guest Editors

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Keywords

  • antineoplastic drugs
  • pharmacokinetics
  • interindividual variability
  • efficacy
  • toxicity
  • therapeutic drug monitoring

Published Papers (1 paper)

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Research

19 pages, 4354 KiB  
Article
A Physiologically-Based Pharmacokinetic Model of Ruxolitinib and Posaconazole to Predict CYP3A4-Mediated Drug–Drug Interaction Frequently Observed in Graft versus Host Disease Patients
by Bettina Gerner, Fatemeh Aghai-Trommeschlaeger, Sabrina Kraus, Götz Ulrich Grigoleit, Sebastian Zimmermann, Max Kurlbaum, Hartwig Klinker, Nora Isberner and Oliver Scherf-Clavel
Pharmaceutics 2022, 14(12), 2556; https://doi.org/10.3390/pharmaceutics14122556 - 22 Nov 2022
Cited by 2 | Viewed by 1574
Abstract
Ruxolitinib (RUX) is approved for the treatment of steroid-refractory acute and chronic graft versus host disease (GvHD). It is predominantly metabolized via cytochrome P450 (CYP) 3A4. As patients with GvHD have an increased risk of invasive fungal infections, RUX is frequently combined with [...] Read more.
Ruxolitinib (RUX) is approved for the treatment of steroid-refractory acute and chronic graft versus host disease (GvHD). It is predominantly metabolized via cytochrome P450 (CYP) 3A4. As patients with GvHD have an increased risk of invasive fungal infections, RUX is frequently combined with posaconazole (POS), a strong CYP3A4 inhibitor. Knowledge of RUX exposure under concomitant POS treatment is scarce and recommendations on dose modifications are inconsistent. A physiologically based pharmacokinetic (PBPK) model was developed to investigate the drug–drug interaction (DDI) between POS and RUX. The predicted RUX exposure was compared to observed concentrations in patients with GvHD in the clinical routine. PBPK models for RUX and POS were independently set up using PK-Sim® Version 11. Plasma concentration-time profiles were described successfully and all predicted area under the curve (AUC) values were within 2-fold of the observed values. The increase in RUX exposure was predicted with a DDI ratio of 1.21 (Cmax) and 1.59 (AUC). Standard dosing in patients with GvHD led to higher RUX exposure than expected, suggesting further dose reduction if combined with POS. The developed model can serve as a starting point for further simulations of the implemented DDI and can be extended to further perpetrators of CYP-mediated PK-DDIs or disease-specific physiological changes. Full article
(This article belongs to the Special Issue Study of Clinical Pharmacokinetics in Oncology Diseases)
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