Effect of renal impairment on arsenic accumulation, methylation capacity, and safety in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide
| العنوان: | Effect of renal impairment on arsenic accumulation, methylation capacity, and safety in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide |
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| المؤلفون: | Meihua Guo, Qilei Zhao, Hongzhu Chen, Xin Hai, Thomas H. Hostetter, Liwang Lin |
| المصدر: | Expert Review of Clinical Pharmacology. 14:1173-1182 |
| بيانات النشر: | Informa UK Limited, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, Acute promyelocytic leukemia, medicine.medical_specialty, Adolescent, Renal function, chemistry.chemical_element, Antineoplastic Agents, Monomethylarsonic acid, Kidney Function Tests, Methylation, Severity of Illness Index, 030226 pharmacology & pharmacy, Gastroenterology, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Arsenic Trioxide, Leukemia, Promyelocytic, Acute, Acute promyelocytic leukemia apl, Internal medicine, medicine, Humans, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, Arsenic trioxide, Arsenic, Aged, Aged, 80 and over, Liver injury, business.industry, General Medicine, Middle Aged, medicine.disease, Long QT Syndrome, chemistry, 030220 oncology & carcinogenesis, Female, Kidney Diseases, Chemical and Drug Induced Liver Injury, business |
| الوصف: | Background: Arsenic trioxide (ATO) was successfully applied to treat acute promyelocytic leukemia (APL).Methods: Inorganic arsenic (iAs), monomethylarsonic acid (MMAV) and dimethyarsinic acid (DMAV) in plasma of 143 APL patients with different renal function were determined. Arsenic methylation capacity was evaluated by iAs%, MMAV%, DMAV%, primary methylation index (PMI, MMAV/iAs), and secondary methylated index (SMI, DMAV/MMAV). Arsenic accumulation with administration frequency were explored. Moreover, safety assessments were performed.Results: Compared with normal renal function, MMAV and DMAV concentrations increased 1.5-4 fold in moderate and severe renal impairment groups, iAs increased 1.3-1.7 fold. APL patients with renal impairment showed lower iAs%, but higher DMAV% and PMI in plasma than those with normal renal function (P < 0.05). MMAV, DMAV, and tAs apparently accumulated with administration frequency in moderate and severe renal dysfunction groups. The incidence of QTc interval prolongation and liver injury increased with the increasing severity of renal impairment.Conclusion: Renal dysfunction may increase exposure to arsenic and arsenic accumulation and affect methylation capacity, then the clinical safety in APL patients treated with ATO. Arsenic-level monitoring and dosing regimen adjustment should be considered in APL patients with moderate and severe renal dysfunction. |
| تدمد: | 1751-2441 1751-2433 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4aec6fe5b6f1f904a7e15d34b5361da6 https://doi.org/10.1080/17512433.2021.1938549 |
| رقم الأكسشن: | edsair.doi.dedup.....4aec6fe5b6f1f904a7e15d34b5361da6 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 17512441 17512433 |
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