Pharmacogenomics in Critical Care: Advancing Precision Medicine for Optimized Drug Therapy and Improved Patient Outcomes

Abstract

Gulfiza Qadir*, Srikanth Jilla, Srimanth Kumar Barigela, Venkata Ramana K, Medavaram Sringala Devijan, B Kishan Sing Naik, Sreelatha Komandur and Qurratulain Hasan

Background Patients in the critical care unit often have complex, acute medical conditions requiring multiple drug regimens. Therapy relies on clinical guidelines and physician experience. This preliminary study evaluated functional polymorphisms in six genes affecting metabolism of drugs often used in ICU patients.

Methods Blood samples from patients of Intensive Care Unit (ICU), Kamineni Hospitals, Hyderabad, India were collected over one month. Genomic DNA was extracted as done routinely for diagnostics. PCR was carried out for a functional variant in six pharmacologically relevant genes—ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5. The PCR products were analysed by Restriction Fragment Length Polymorphism (RFLP) or Sanger sequencing. The genotypes identified were categorized as normal, intermediate and poor metabolizers.

Results The 41 patient samples showed significant genotypic variation with 29% who were poor transporters for ABCB1 (rs1045642), while 41% of them were poor metabolizers for CYP2B6 (rs3745274). Around 75% of samples had a genotype for CYP2C9 (rs1057910) which indicated normal metabolizers. 20% and 41% poor metabolizers were seen for CYP2C19 (rs4244285) and CYP3A5 (rs776746), respectively. Whereas CYP3A4 (rs2740574) had no poor metabolizers. These variations are responsible for the metabolism of commonly used ICU drugs like proton pump inhibitors, anticoagulants, antiepileptics, antibiotics, analgesics, etc.

Conclusion This preliminary study indicates that a significant proportion of ICU patients would benefit from pharmacogenomic testing as 20-40% of the individuals exhibited genotypes associated with poor metabolism that may require dosage regulation. A larger study is warranted to develop appropriate panels for different types of patients admitted to ICU.

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