(1) Background: In clinical settings, data regarding sex are rarely investigated. In women, factors such as body size and composition, hormonal variations, metabolism, and access to care systems and therapy could strongly influence the pharmacological management and the outcome of the therapy. To underline this sex-related difference, we retrospectively collected data from adrenocortical carcinoma patients treated with mitotane, and then evaluated sex-related pharmacokinetics parameters. (2) Methods: A fully validated chromatographic method was used to quantify mitotane concentration in plasma collected from adult patients, also considering the active metabolite ortho,para,dichlorodiphenylethene (o,p′-DDE). Statistical analyses were used to evaluate the sex influence on drugs pharmacokinetics. (3) Results: We found that sex resulted as predictive factor of plasma mitotane and o,p′-DDE concentrations and significantly influenced the attainment of the therapeutic target of mitotane, implying that female sex could be a risk factor of treatment failure. (4) Conclusions: These results suggest that mitotane therapy should be modulated according to patient sex. Furthermore, the proposed approach could contribute to facilitating and disseminating sex-specific pharmacology.

Sex Differences on Mitotane Concentration and Treatment Outcome in Patients with Adrenocortical Carcinoma

Allegra, Sarah
First
;
Puglisi, Soraya;Brescia, Irene;Basile, Vittoria;Calabrese, Anna;Reimondo, Giuseppe;De Francia, Silvia
Last
2021

Abstract

(1) Background: In clinical settings, data regarding sex are rarely investigated. In women, factors such as body size and composition, hormonal variations, metabolism, and access to care systems and therapy could strongly influence the pharmacological management and the outcome of the therapy. To underline this sex-related difference, we retrospectively collected data from adrenocortical carcinoma patients treated with mitotane, and then evaluated sex-related pharmacokinetics parameters. (2) Methods: A fully validated chromatographic method was used to quantify mitotane concentration in plasma collected from adult patients, also considering the active metabolite ortho,para,dichlorodiphenylethene (o,p′-DDE). Statistical analyses were used to evaluate the sex influence on drugs pharmacokinetics. (3) Results: We found that sex resulted as predictive factor of plasma mitotane and o,p′-DDE concentrations and significantly influenced the attainment of the therapeutic target of mitotane, implying that female sex could be a risk factor of treatment failure. (4) Conclusions: These results suggest that mitotane therapy should be modulated according to patient sex. Furthermore, the proposed approach could contribute to facilitating and disseminating sex-specific pharmacology.
11
3
266
276
https://doi.org/10.3390/life11030266
AAC; o,p0-DDD; o,p0-DDE; TDM; gender
Allegra, Sarah; Puglisi, Soraya; Brescia, Irene; Chiara, Francesco; Basile, Vittoria; Calabrese, Anna; Reimondo, Giuseppe; De Francia, Silvia
File in questo prodotto:
File Dimensione Formato  
life-11-00266-v2.pdf

Accesso aperto

Tipo di file: PDF EDITORIALE
Dimensione 1.35 MB
Formato Adobe PDF
1.35 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1782701
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 5
social impact