Postmarketing assessment of a switchable similar anastrozole product in Brazilian breast cancer patients

ABSTRACT

Several formulations of the aromatase inhibitor anastrozole are available in Brazil. We carried out a postmarketing surveillance of the anastrozole (test) formulation in current use at the Brazilian National Cancer Institute (INCA), by comparing anastrozole through plasma concentrations obtained with the test versus the reference formulation. Thirty-three postmenopausal breast cancer patients participated in an open label, bracketed protocol, comprising 3 successive phases of 8-10 days each. The test formulation was used in phases 1 and 3 and the reference formulation in phase 2. Blood samples were collected in the last 2 days of each phase for LC-MS/MS quantification of anastrozole concentration in plasma. Through anastrozole concentrations ranged between 17.4-86.9ng/ml across the three phases, with median (interquartile ranges) values of 43.7 (37.2-52.7), 41.3 (30.9-50.7) and 43.3 (33.9-55.8) ng/ml in phases 1, 2 and 3, respectively. ANOVA detected no statistically significant difference in anastrozole plasma concentrations across the three phases, consistent with switchability between the reference and test formulations. The genetic component (r_GC) of through anastrozole plasma concentrations, estimated using the repeated drug administration procedure across the three phases, was 0.94, suggesting an important component of genetic variability in anastrozole pharmacokinetics.

RESUMO

Várias formulações do inibidor de aromatase anastrozol estão disponíveis no Brasil. Realizamos uma avaliação farmacocinética pós-comercialização da formulação (teste) de anastrozol em uso corrente no Instituto Nacional do Câncer (INCA), por meio de comparação das concentrações plasmáticas de anastrozol obtidas com a formulação teste versus a formulação de referência. Trinta e três pacientes com câncer de mama na pós-menopausa participaram de um protocolo aberto, compreendendo 3 fases sucessivas de 8 a 10 dias cada. A formulação teste foi utilizada nas fases 1 e 3 e a formulação de referência na fase 2. Amostras de sangue foram coletadas nos Ultimos 2 dias de cada fase para quantificação por LC-MS/MS da concentração de anastrozol no plasma. As concentrações de vale de anastrozol variaram entre 17,4-86,9ng/ml nas três fases, com valores medianos (intervalos interquartis) de 43,7 (37,2-52,7), 41,3 (30,9-50,7) e 43,3 (33,9-55,8) ng/ml nas fases 1, 2 e 3, respectivamente. ANOVA não detectou nenhuma diferença estatisticamente significativa entre as concentrações de anastrozol nas três fases, consistente com a intercambialidade entre as formulações teste e de referência. O componente genético (r_CG) das concentrações plasmáticas de anastrozol, estimado usando o procedimento de administração repetida do medicamento nas três fases, foi de 0,94, sugerindo importante variabilidade genética na farmacocinética do anastrozol.

Keywords:

Aromatase inhibitors - Anastrozole - Breast neoplasms

Descritores:

Inibidores de aromatase - Anastrozol - Neoplasias mamárias

Publication History

Received: 28 October 2022

Accepted: 25 November 2022

Article published online:
05 January 2023

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