Circannual variation of mitotane and its metabolites plasma levels in patients with adrenocortical carcinoma.

Abstract

OBJECTIVES:

Mitotane is the reference drug for the adrenocortical carcinoma treatment; its pharmacological activity seems to depend on drug transformation in two active metabolites: o,p'-DDE (dichlorodiphenylethene) and o,p'-DDA (dichlorodiphenylacetate). Mitotane and metabolites are lipophilic agents; thus, they tend to accumulate into adipose tissues (white and brown), which change their prevalence seasonally. Aim of the work was to evaluate mitotane and metabolites plasma levels variation over the year, in adrenocortical cancer patients treated with Lysodren® for at least 6 months.

METHODS:

We enrolled a group of 86 adrenocortical carcinoma diagnosed patients, who underwent radical surgery and started mitotane as adjuvant treatment. For drug and metabolites plasma level (from samples collected ~12 h after the dose administration of mitotane, just before the subsequent administration) determination, a validated chromatographic method was used.

KEY FINDINGS:

Results showed an evidence of a seasonal trend for the three substance (o,p'-DDD, o,p'-DDE and o,p'-DDA) plasma levels, in terms of acrophases and lower values. Furthermore, it came out that male patients need a higher significant mitotane drug dose than female patients to reach mitotane therapeutic window.

CONCLUSIONS:

In conclusion, this is the first study assessing a mitotane plasma level variation over the year, but further studies in larger cohorts are required.

• Authors: Jessica Cusato, Silvia De Francia, Sarah Allegra, Simona Carrella, Elisa Pirro, Francesca Maria Piccione, Francesca De Martino, Anna Ferrero, Fulvia Claudia Daffara, Massimo Terzolo, Alfredo Berruti, Francesco Di Carlo, Marco Tampellini, Antonio D'Avolio
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 69 Issue 11 Pg. 1524-1530 (Nov 2017) ISSN: 2042-7158 [Electronic] England
• PMID: 28809444 (Publication Type: Journal Article)
• Copyright: © 2017 Royal Pharmaceutical Society.

Chemical References

• Antineoplastic Agents, Hormonal
• 2,2-(2-chlorophenyl-4'-chlorophenyl)acetic acid
• Mitotane
• 2,2-(2-chlorophenyl-4'-chlorophenyl)-1,1-dichloroethene

Topics

• Adipose Tissue (metabolism)
• Adrenal Cortex Neoplasms (therapy)
• Adrenocortical Carcinoma (therapy)
• Adult
• Antineoplastic Agents, Hormonal (administration & dosage, pharmacokinetics)
• Chemotherapy, Adjuvant (methods)
• Chromatography, High Pressure Liquid (methods)
• Female
• Humans
• Male
• Middle Aged
• Mitotane (administration & dosage, analogs & derivatives, pharmacokinetics)
• Seasons
• Sex Factors
• Time Factors
• Young Adult