A Physiologically Based Pharmacokinetic Model to Predict Systemic Ondansetron Concentration in Liver Cirrhosis Patients.

Autor: Alqahtani F; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Alruwaili AH; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Alasmari MS; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Almazroa SA; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Alsuhaibani KS; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Rasool MF; Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan., Alruwaili AF; Clinical Pharmacy Unit, Department of Pharmaceutical Services, Dallah Hospital, Riyadh 12381, Saudi Arabia., Alsanea S; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Dec 06; Vol. 16 (12). Date of Electronic Publication: 2023 Dec 06.
DOI: 10.3390/ph16121693
Abstrakt: Introduction: Ondansetron is a drug that is routinely prescribed for the management of nausea and vomiting associated with cancer, radiation therapy, and surgical operations. It is mainly metabolized in the liver, and it might accumulate in patients with hepatic impairment and lead to unwanted adverse events.
Methods: A physiologically based pharmacokinetic (PBPK) model was developed to predict the exposure of ondansetron in healthy and liver cirrhosis populations. The population-based PBPK simulator PK-Sim was utilized for simulating ondansetron exposure in healthy and liver cirrhosis populations.
Results: The developed model successfully described the pharmacokinetics of ondansetron in healthy and liver cirrhosis populations. The predicted area under the curve, maximum systemic concentration, and clearance were within the allowed twofold range. The exposure of ondansetron in the population of Child-Pugh class C has doubled in comparison to Child-Pugh class A. The dose has to be adjusted for liver cirrhosis patients to ensure comparable exposure to a healthy population.
Conclusion: In this study, the developed PBPK model has described the pharmacokinetics of ondansetron successfully. The PBPK model has been successfully evaluated to be used as a tool for dose adjustments in liver cirrhosis patients.
Databáze: MEDLINE
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