Comparative preclinical pharmacokinetics study of 3,3′-diindolylmethane formulations: is personalized treatment and targeted chemoprevention in the horizon?

EPMA Journal

Olga Pchelintseva⁴  Igor Kuznetsov²  Vadim Drukh⁴  Ekaterina Muyzhnek³  Vsevolod Kiselev⁴  Mikhail Paltsev¹ 

[1] National Research Centre (NRC “Kurchatov Institute”), 1, Akademika Kurchatova Pl., Moscow 123182, Russia;Moscow State Medical Stomatological University (MGMSU), Delegatskaya St., 2/1, Moscow 127473, Russia;ZAO “MiraxBioPharma”, 12 Kutuzovsky av., Moscow 121248, Russia;Peoples’ Friendship University of Russia, Miklukho-Maklaya St., 6, Moscow 117198, Russia

关键词: BRCA1;    Breast cancer;    Personalized medicine;    Targeted prevention;    Molecularly targeted treatment;    Bioavailability;    Pharmacokinetics;    Preclinical trials;    3′-Diindolylmethane;    3;   

Others  :  801255
DOI  :  10.1186/1878-5085-4-25

 received in 2013-10-10, accepted in 2013-11-14,  发布年份 2013

【 摘 要 】

Background

3,3′-Diindolylmethane (DIM) is known as an agent of natural origin that provides protection against different cancers due to the broad spectrum of its biological activities in vivo. However, this substance has a very poor biodistribution and absorption in animal tissues. This preclinical trial was conducted to evaluate the pharmacokinetics and bioavailability of various DIM formulations in animal model.

Materials and methods

The pharmacokinetic parameters of one crystalline DIM formulation and one liquid DIM formulation (oil solution) compared to non-formulated crystalline DIM (control) were tested in 200 rats. The formulations were orally administered to animals by gavage at doses of 200 mg/kg per DIM (crystalline DIM formulation and non-formulated crystalline DIM) and 0.1 mg/kg per DIM (DIM in oil solution). DIM plasma elimination was measured using HPLC method; after that, the area under the curve (AUC), relative bioavailability, and absolute bioavailability were estimated for two formulations in relation to non-formulated crystalline DIM.

Results and conclusion

The highest bioavailability was achieved by administering liquid DIM (oil solution), containing cod liver oil and polysorbate. The level of DIM in rat blood plasma was about fivefold higher, though the 2,000-fold lower dose was administered compared to crystalline DIM forms. The novel pharmacological DIM substance with high bioavailability may be considered as a promising targeted antitumor chemopreventive agent. It could be used to prevent breast and ovarian cancer development in patients with heterozygous inherited and sporadic BRCA1 gene mutations. Further preclinical and clinical trials are needed to prove this concept.

【 授权许可】

   
2013 Paltsev et al.; licensee BioMed Central Ltd.

【 图 表 】

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