Marta Gontijo de Aguiar1, José Eduardo Gonçalves1, Mirna d'Auriol Souza2, Rosiana Estefáne de Silva3, Josianne Nicacio Silveira2, Gláucia Cota3. 1. Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 2. Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 3. Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Centro de Referência em Leishmanioses, Pesquisa Clínica e Políticas Públicas em Doenças Infecto-Parasitárias, Belo Horizonte, MG, Brazil.
Abstract
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 (C1 h ), area under curve of drug concentration in plasma from zero to 6 h (AUC0-6 h ) 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 C1 h 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, C1 h and AUC(0-6 h) 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.
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 (C1 h ), area under curve of drug concentration in plasma from zero to 6 h (AUC0-6 h ) 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 C1 h 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, C1 h and AUC(0-6 h) 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.
Authors: Diana J Garay-Baquero; David E Rebellón-Sánchez; Miguel D Prieto; Lina Giraldo-Parra; Adriana Navas; Sheryl Atkinson; Stuart McDougall; Maria Adelaida Gómez Journal: Bioanalysis Date: 2021-04-08 Impact factor: 2.695