Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Trop Med Int Health. 2018 Oct;23(10):1110-1117. doi: 10.1111/tmi.13130. Epub 2018 Aug 14.
OBJECTIVES: To evaluate the antimony (Sb) in plasma of patients who underwent a standardised meglumine antimoniate (MA) intralesional infiltration protocol for cutaneous leishmaniasis treatment. METHODS: The level of Sb in plasma was determined by atomic absorption spectroscopy, before and 1, 2, 4 and 6 hours after the first intralesional infiltration of MA to determine the parameters peak concentrations (C ) area under curve of drug concentration in plasma from zero to 6 h (AUC ) and elimination half-life (t½) of Sb. Blood samples were also collected weekly during the treatment period, always before infiltration. RESULTS: Fourteen patients underwent MA intralesional infiltration with doses ranging from 0.8 to 9 mg Sb/kg at the first infiltration. The C ranged from 3850 to 47 095 mg × h/L and was the highest concentration obtained for 11 of 14 patients after the first intralesional infiltration of MA. A rapid initial phase of distribution lasting up to 4 h (2.6 ± 0.34 h) was followed by a slower elimination phase. Total skin lesion area, C and AUC were related to the dose of Sb infiltered (P < 0.05). Plasma Sb in samples collected weekly before the infiltration revealed antimony concentrations below the quantification limit (15.0 μg Sb/l) during the treatment period. CONCLUSIONS: Sb is quickly absorbed and eliminated after intralesional administration of MA, in a pattern similar to that reported with the Sb systemic administration. Using a therapeutic schedule limited to weekly intralesional infiltration of doses <10 mg Sb/kg does not result in plasma Sb accumulation.
目的:评估接受标准化葡甲胺锑(MA)瘤内渗透方案治疗皮肤利什曼病的患者血浆中的锑(Sb)含量。
方法:在第一次 MA 瘤内渗透前、后 1、2、4 和 6 小时,通过原子吸收光谱法测定血浆中 Sb 的水平,以确定峰值浓度(C)、血浆药物浓度从 0 到 6 小时的曲线下面积(AUC)和 Sb 的消除半衰期(t½)等参数。在治疗期间,每次渗透前也每周采集血液样本。
结果:14 名患者接受 MA 瘤内渗透治疗,剂量范围为 0.8 至 9 mg Sb/kg。C 范围为 3850 至 47095 mg × h/L,14 名患者中有 11 名在第一次 MA 瘤内渗透后获得最高浓度。快速分布初始阶段持续 4 小时(2.6 ± 0.34 小时),随后是较慢的消除阶段。总皮肤病变面积、C 和 AUC 与渗透的 Sb 剂量相关(P < 0.05)。在渗透前每周采集的血浆 Sb 样本中,在治疗期间发现 Sb 浓度低于定量下限(15.0 μg Sb/l)。
结论:MA 瘤内给药后,Sb 迅速吸收和消除,其模式与 Sb 全身给药相似。使用每周一次、剂量<10 mg Sb/kg 的瘤内渗透治疗方案不会导致血浆 Sb 积累。
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