Acta Studiorum Medicorum et Biomedicorum

Open-access, peer-reviewed journal edited by Apostolos Zarros and published semiannually by St Cuthbert Press Ltd (Stanley, England, UK)

ISSN (print): 2977-6295
ISSN (online): 2977-6309

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Acta Stud. Med. Biomed.

1(2): 43–49 (2025)

RESEARCH REPORT | open access

Pharmacodynamics of cisplatin, methotrexate, and doxorubicin in an in vitro pharmacokinetics / pharmacodynamics model employing T24 human bladder cancer cells: the role of albumin under single administration-simulating conditions

Suhad Hussein Atshan, Hussam W. Al-Humadi*

Department of Pharmacology, College of Medicine, University of Babylon, Hillah, Iraq (SHA) ▪ College of Pharmacy, University of Babylon, Hillah, Iraq (HWA)
*corresponding author (alhumadi2010@gmail.com; phar.hussam.wahab@uobabylon.edu.iq)

Received: 19 August 2025; Revised: 28 August 2025; Accepted: 29 August 2025; Published: 02 September 2025

DOI: 10.5281/zenodo.17034069

Full-text article: PDF

Abstract: Background: Bladder cancer, predominantly urothelial carcinoma, is a common malignancy. Despite the range of available treatments, recurrence and resistance remain significant challenges, thereby underscoring the need for the development of predictive in vitro pharmacokinetics / pharmacodynamics (PK/PD) models in order to optimize therapies. Aim: This study aimed at exploring the cytotoxic efficacy of three established anticancer agents (namely cisplatin, methotrexate, and doxorubicin) against T24 human bladder cancer cells, while using a novel in vitro PK/PD model. A key objective was to analyse the impact of 5% human albumin (simulating plasma protein binding) on each drug’s cytotoxic efficacy, over a 72-h period. Methodology: A dynamic, peristaltic pump-based in vitro PK/PD system was employed, while cell growth inhibition was assessed spectrophotometrically using the reduction of the relative optical density at 630 nm as a surrogate for cell viability. Dose–response analyses were conducted for each drug at five different concentrations, in the absence and presence of 5% human albumin. Data were fitted to the E_max model and were validated with R² values. Results: All three of the herein assessed drugs (cisplatin, methotrexate, and doxorubicin) demonstrated a significant and concentration-dependent inhibition of T24 proliferation, with highest efficacies exhibited by cisplatin (followed by methotrexate then doxorubicin); all confirming a strong fit to the E_max model. The addition of albumin caused a plateauing effect in the obtained dose–response curves for all of the assessed chemotherapeutic agents, thereby indicating a reduced free drug availability due to protein binding, without completely abolishing the drug efficacy. Conclusion: This study established a robust in vitro PK/PD model for simulating drug effects on T24 cells, with the presence of albumin modulating the drug efficacy by limiting the free drug concentrations in the medium.

Keywords: albumin; cisplatin; bladder cancer; doxorubicin; methotrexate

Atshan S. H., Al-Humadi H. W.: Pharmacodynamics of cisplatin, methotrexate, and doxorubicin in an in vitro pharmacokinetics / pharmacodynamics model employing T24 human bladder cancer cells: the role of albumin under single administration-simulating conditions. Acta Stud. Med. Biomed. 1(2): 43–49 (2025).
https://doi.org/10.5281/zenodo.17034069

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