ساخت اکانت کاربری رایگان

مقالات پذیرفته شده کنگره

  • صفحه نخست
  • مقالات پذیرفته شده اولین کنگره بین المللی فارماکوژنتیک
بازنشر

  • Professor

  • Negar Firouzabadi,1,* Soliman Mohammadi Samani,2 Dorsa Karbasi,3 Parisa Ghasemiyeh,4 Nahid Alimoradi,5 Maryam Kavousi,6
    1. Shiraz University of Medical Sciences
    2. Shiraz University of Medical Sciences
    3. Shiraz University of Medical Sciences
    4. Shiraz University of Medical Sciences
    5. Kermanshah University of Medical Sciences
    6. Erasmus MC University Medical Centre Rotterdam


  • Introduction: Vancomycin a commonly administered antibiotic for various Gram-positive infections in critically ill patients has a narrow therapeutic index and its main adverse drug reaction is acute kidney injury (AKI). Higher vancomycin trough concentration and area under the curve (AUC) values would be associated with higher rates of AKI. Therefore, dose adjustment based on targeted pharmacokinetic values would be essential to avoid toxicity and achieve optimal clinical response. However, there are numerous reports regarding the discrepancy between pharmacokinetic parameter values and AKI. In this regard, we examined the possible role of pharmacogenetics in vancomycin-induced AKI to distinguish patients who are genetically prone to AKI.
  • Methods: The sample size was selected as 88 patients with power of 80% and alpha of 0.05. In this regard, a total of 92 critically ill patients who were admitted to the ICU wards in the two hospitals and were receiving vancomycin were screened. EDTA blood samples were collected from each participant, and genomic DNA was extracted from whole blood leukocytes using the salting out extraction method with slight modification. The polymorphisms rs1126616, rs429358, and rs7412 were analyzed via the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Blood samples were prepared from the patients at the steady state condition, just before the fifth dose administration. Vancomycin was extracted from the plasma samples and analysed through the validated high performance liquid chromatography (HPLC) method according to our previous studies.
  • Results: The results indicated a significant difference in OPN and APOE genotype distribution between AKI and non-AKI patients (P=0.001 and 0.02, respectively). Stepwise multivariate logistic regression analysis showed that patients with e2e3 genotype were 4.2-fold more prone to AKI (P=0.029; OR=4.2; 95%CI=1.2-15.7). Moreover, there was a significant correlation between pharmacokinetic parameters (calculated trough concentration, AUCτ, AUC24h, and t1/2) and vancomycin-induced AKI.
  • Conclusion: Genotyping the patients for OPN and APOE polymorphisms before vancomycin initiation would be promising as a routine clinical practice to obtain an efficient clinical response and prevent vancomycin-induced AKI, especially in critically ill patients.
  • Keywords: Vancomycin; Acute kidney injury; Pharmacogenetics; Osteopontin; Apolipoprotein

به خانواده بزرگ فارماکوژنتیک و فارماکوژنومیکس بپیوندید!

ایجاد حساب کاربری رایگان