Solid-phase extraction and high-performance liquid chromatographic determination of tamoxifen and its major metabolites in plasma

MacCallum, J.; Cummings, Jeffrey L.; Dixon, J. Michael; Miller, W. R.

doi:10.1016/0378-4347(95)00530-7

Cited by 43 publications

(30 citation statements)

References 28 publications

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“…Like other pharmaceuticals, tamoxifen can enter the aquatic environment in its native form or as transformed excretory products. Tamoxifen is light-sensitive and extensively metabolized, although certain metabolites such as 4-hydroxytamoxifen are capable of highaffinity ER binding (MacCallum et al, 1996). In a study of the environmental occurrence of tamoxifen conducted in the UK, concentrations ranged from 0.146 to 0.369 g/l in sewage effluents and the parent compound was not degraded in the sewage treatment plant (Fent et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen effects on the early life stages and reproduction of Japanese medaka (Oryzias latipes)

Sun

Zha

Spear

et al. 2007

Environmental Toxicology and Pharmacology

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Tamoxifen is widely used in the treatment of breast cancer and can enter the aquatic environment in municipal wastewater. To evaluate potential effects on embryonic development of Japanese medaka, fertilized eggs were exposed to tamoxifen at 1-625 g/l for 14 days. Adverse effects on hatchability and time to hatching only occurred at 125 and 625 g/l. Reproductive effects were assessed by exposing adults for 21 days to the same dose range. At all concentrations tested, tamoxifen significantly increased plasma vitellogenin levels in males in a dose-dependent manner. Fecundity and fertility were detrimentally affected at 625 g/l. Additionally, F1 eggs were removed from tamoxifen-contaminated water to evaluate transgenerational effects. Hatchability was affected at 625 g/l but no morphological deformities were observed. A significant dose-dependent increase in the proportion of genotypic males occurred at all concentrations greater than 5 g/l.

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Section: Discussionmentioning

confidence: 99%

Tamoxifen effects on the early life stages and reproduction of Japanese medaka (Oryzias latipes)

Sun

Zha

Spear

et al. 2007

Environmental Toxicology and Pharmacology

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“…Therefore, OHTAM requires a threefold higher concentration to induce the same hemolytic effect observed for TAM and the hemolysis takes longer, pointing out that OHTAM shows a much weaker hemolytic action than TAM. Considering that the tissue and serum concentrations of OHTAM are much lower as compared with TAM (Lien et al, 1987(Lien et al, , 1991MacCallum et al, 1996), OHTAM may not reach concentrations high enough to cause hemolysis, suggesting that this drug does not contribute to TAM-induced hemolytic anemia.…”

Section: Discussionmentioning

confidence: 99%

“…Actually, the anti-estrogenic and antiproliferative activities of OHTAM in vitro are much stronger as compared with TAM (Borgna and Rochefort, 1981;Etienne et al, 1989), but the pharmacological relevance of OHTAM has been questioned (McCague et al, 1990) due to its low serum concentrations (Lien et al, 1987;MacCallum et al, 1996). However, the strong affinity of OHTAM for biomembrane proteins (Custo´dio et al, 1991) and its higher partitioning in the lipid bilayer as compared with TAM (Custo´-dio et al, 1991), perturbing the membrane lipid-protein interface (Custo´dio et al, 1993b) suggest that OHTAM may accumulate in tissues, reaching there the required effective concentrations for its cytotoxic effects, as described by Lien et al (1991).…”

Section: Introductionmentioning

confidence: 99%

Hydroxytamoxifen interaction with human erythrocyte membrane and induction of permeabilization and subsequent hemolysis

Silva

Madeira

Almeida

et al. 2001

Toxicology in Vitro

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4-Hydroxytamoxifen (OHTAM) is the most active metabolite of the widely prescribed anticancer drug tamoxifen (TAM) used in breast cancer therapy. This work describes the effects of OHTAM on isolated human erythrocytes, using standardized test conditions, to check for a putative contribution to the TAM-induced hemolysis and to study basic mechanisms involved in the interaction of OHTAM with cell membranes. Incubation of isolated human erythrocytes with relatively high concentrations of OHTAM results in a concentration-dependent hemolysis, its hemolytic effect being about one-third of that induced by TAM. OHTAMinduced hemolysis is prevented by either a-tocopherol (a-T) or a-tocopherol acetate (a-TAc) and it occurs in the absence of oxygen consumption and hemoglobin oxidation, ruling out the oxidative damage of erythrocytes. However, OHTAM remarkably increases the osmotic fragility of erythrocytes, increasing the susceptibility of erythrocytes to hypotonic lysis. Additionally, the hemoglobin release induced by OHTAM is preceded by a rapid efflux of intracellular K + . Therefore, our data suggest that OHTAM-induced hemolysis does not contribute to TAM-induced hemolytic anemia and it is a much weaker toxic drug as compared with TAM. Moreover, at variance with the membrane disrupting effects of TAM, OHTAM promotes perturbation of the membrane's backbone region due to its strong binding to proteins with consequent formation of membrane paths of permeability to small solutes and retention of large solutes like hemoglobin, followed by osmotic swelling and cell lysis. The prevention of OHTAM-induced hemolysis by a-T and a-TAc is probably committed to the permeability sealing resulting from structural stabilization of membrane. #

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“…Studies have demonstrated that letrozole has superior efficacy to tamoxifen for endocrine therapy, and is likely to be an alternative or complement of the latter in the clinical use (Brodie et al, 1999;Nunez et al, 2004). Furthermore, since tamoxifen is light-sensitive and extensively metabolized (MacCallum et al, 1996) while letrozole is more stable, the potential of letrozole to pose a risk in the environment is greater.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of the aromatase inhibitor letrozole to Japanese medaka (Oryzias latipes) eggs, larvae and breeding adults

Sun

Zha

Spear

et al. 2007

Comparative Biochemistry and Physiology Part C: Toxicology &

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Solid-phase extraction and high-performance liquid chromatographic determination of tamoxifen and its major metabolites in plasma

Cited by 43 publications

References 28 publications

Tamoxifen effects on the early life stages and reproduction of Japanese medaka (Oryzias latipes)

Tamoxifen effects on the early life stages and reproduction of Japanese medaka (Oryzias latipes)

Hydroxytamoxifen interaction with human erythrocyte membrane and induction of permeabilization and subsequent hemolysis

Toxicity of the aromatase inhibitor letrozole to Japanese medaka (Oryzias latipes) eggs, larvae and breeding adults

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