Genetic Polymorphisms influencing Low Posaconazole Plasma Concentration in Patients with Hematologic malignancies
| Autor: | Ji Whan Bang, Pyeong-Gyun Choe, Kyoung Ho Song, Eu Suk Kim, Myoung Don Oh, Wan Beom Park, Hyeon Jeong Suh, Nam Joong Kim, Hong Bin Kim, Eun Young Lee, Sang Won Park |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Posaconazole business.industry 030106 microbiology Hematologic Neoplasms Gastroenterology 03 medical and health sciences Infectious Diseases Oncology Plasma drug concentration Internal medicine Plasma concentration medicine In patient Allele business Whole blood medicine.drug |
| Zdroj: | Open Forum Infectious Diseases. 4:S295-S295 |
| ISSN: | 2328-8957 |
| Popis: | Background There are poor absorbers for posaconazole oral suspension who show low posaconazole plasma concentration (PPC) despite increased dosage. Posaconazole metabolism is mediated mainly by the UDP-glucuronosyltransferase (UGT) enzyme, especially the enzyme UGT1A4. The aim of this study was to investigate the effects of genetic polymorphisms on the PPC. Methods This prospective study was conducted from September 2014 to August 2016. We enrolled patients with acute myeloid leukemia or myelodysplastic syndrome who received a posaconazole oral suspension of 200 mg three times daily for fungal prophylaxis. The steady-state PPC on day 8 was measured by liquid chromatography-tandem mass spectrometry. The multi-drug resistance gene 1 C3435T and G2677T/A variations, and UGT1A4*3b were examined by direct sequencing of DNA from peripheral whole blood samples. We defined the poor absorbers as those with PPC Results In the study period, 155 patients were enrolled. The median age of patients was 56 years (interquartile range, 44–64 years), and 54.2% were man. Six patients (3.9%) were defined as poor absorbers and 57 patients (36.8%) did not reach the optimal PPC on day 8. In multivariate analysis, the independent risk factors for poor absorber were at least 1 UGT1A4*3b allele (adjusted odds ratio [aOR], 7.756; 95% confidence interval [CI], 1.034–58.152; P = 0.046) and poor oral intake (aOR per 100 kcal, 0.727; 95% CI, 0.555–0.953; P = 0.021). There was no statistically significant association between the genetic polymorphisms and the optimal PPC on day 8. Conclusion The UGT1A14*3b polymorphism is an independent risk factor for poor absorbers for posaconazole oral suspension in patients with hematologic malignancies. Disclosures All authors: No reported disclosures. |
| Databáze: | OpenAIRE |
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