Tropical medicine & international health : TM & IH · 2018
Plasma antimony determination during cutaneous leishmaniasis treatment with intralesional infiltration of meglumine antimoniate.
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de Aguiar Marta Gontijo, Gonçalves José Eduardo, Souza Mirna d'Auriol, de Silva Rosiana Estefáne, Silveira Josianne Nicacio, Cota Gláucia
Аннотация
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.
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.