Circannual variation of mitotane and its metabolites plasma levels in patients with adrenocortical carcinoma. in The Journal of pharmacy and pharmacology / J Pharm Pharmacol. 2017 Nov;69(11):1524-1530. doi: 10.1111/jphp.12798. Epub 2017 Aug 15.
2017
AOU San Luigi di Orbassano
ASL Città di Torino
Tipo pubblicazione
Journal Article
Autori/Collaboratori (14)Vedi tutti...
Tampellini M
Division of Oncology, Department of Oncology, "San Luigi" Hospital-Orbassano, University of Turin, Orbassano, TO, Italy.
Di Carlo F
Department of Biological and Clinical Sciences, S. Luigi Gonzaga Hospital, University of Turin, Orbassano, TO, Italy.
Berruti A
Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, Spedali Civili Hospital, University of Brescia, Brescia, Italy.
et alii...
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.
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PMID : 28809444
DOI : 10.1111/jphp.12798
Keywords
seasons; gender medicine; adrenocortical carcinoma; Therapeutic Drug Monitoring; HPLC; DDD; Young Adult; Sex Factors; Time Factors; Seasons; Mitotane/administration & dosage/analogs & derivatives/pharmacokinetics; Middle Aged; Male; Female; Humans; Chromatography, High Pressure Liquid/methods; Chemotherapy, Adjuvant/methods; Antineoplastic Agents, Hormonal/administration & dosage/pharmacokinetics; Adult; Adrenocortical Carcinoma/therapy; Adrenal Cortex Neoplasms/therapy; Adipose Tissue/metabolism;