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Evaluation of pentamidine tolerability and efficacy between CYP2C19 phenotypes.
Alexis Koon1, Jiaxian He2, Jai Patel3
1Rosalind Franklin University of Medicine & Science, College of Pharmacy, North Chicago, IL 60064, USA.
Pharmacogenomics
|October 17, 2023
Summary
This study found no link between CYP2C19 genetic variations and side effects leading to discontinuation of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in stem cell transplant patients.
Area of Science:
- Pharmacogenetics
- Hematopoietic Stem Cell Transplantation
- Infectious Disease Prophylaxis
Background:
- Intravenous pentamidine is a key prophylactic agent against Pneumocystis jirovecii pneumonia (PJP) in hematopoietic stem cell transplant (HSCT) recipients.
- Pentamidine metabolism involves CYP2C19, an enzyme subject to significant pharmacogenetic variability.
- Understanding the impact of CYP2C19 phenotype on pentamidine tolerability is crucial for optimizing PJP prophylaxis in HSCT patients.
Purpose of the Study:
- To investigate the association between CYP2C19 phenotype and the discontinuation of intravenous pentamidine due to drug-related side effects.
- To evaluate the incidence of pentamidine discontinuation and PJP in allogeneic HSCT patients based on CYP2C19 pharmacogenetic profiles.
Main Methods:
- Retrospective analysis of 81 allogeneic HSCT patients receiving intravenous pentamidine for PJP prophylaxis.
- Classification of patients into CYP2C19 phenotype groups.
- Univariate logistic regression analysis to assess the association between CYP2C19 phenotype and pentamidine discontinuation due to side effects.
Main Results:
- A total of 10 patients (12.3%) discontinued pentamidine due to side effects.
- No statistically significant difference in pentamidine discontinuation rates was observed between different CYP2C19 phenotype groups (p=0.18).
- Similarly, no significant association was found between CYP2C19 phenotype and the occurrence of pentamidine-related side effects (p=0.475).
Conclusions:
- The study found no significant association between CYP2C19 phenotype and the discontinuation of intravenous pentamidine due to side effects in HSCT recipients.
- Both drug discontinuation and PJP infection rates were low in this cohort, suggesting good overall tolerability and efficacy of pentamidine prophylaxis.
- Further research may explore other factors influencing pentamidine tolerability in this vulnerable patient population.
Keywords:
CYP2C19Pneumocystis jirovecii pneumoniaallogeneic hematopoietic stem cell transplanthematopoietic stem cell transplantpentamidineMore Related Videos
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