• Title/Summary/Keyword: tamoxifen

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Effects of mixed formulation of tamoxifen and blue honeysuckle on the pharmacokinetics profiles of tamoxifen after single oral administration

  • Hu, Jin-Ryul;Jang, Tae-Woo;Kang, Su-Jin;Ku, Sae-Kwang;Choi, Seong-Hun;Lee, Young-Joon
    • The Journal of Korean Medicine
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    • v.40 no.4
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    • pp.1-15
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    • 2019
  • Objectives: Here, we investigated the effects of concentrated and lyophilized powders Blue honeysuckle (BH) on the PK of tamoxifen, to establish the pharmacokinetics (PK) profiles as one of essential process in new drug development. Methods: After single oral treatment of 0.4 mg/ml of tamoxifen or tamoxifen 0.4 with BH 40, 20 and 10 mg/ml, the plasma were collected at 0.5 hr before administration, 0.5, 1, 2, 3, 4, 6, 8 and 24 hr after end of single or mixed formula treatment. Plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. Tmax, Cmax, AUC, t1/2 and MRTinf were analyzed using noncompartmental PK data analyzer programs. Results: Tamoxifen and BH 40 mg/ml did not induce any significant change on the plasma tamoxifen concentrations, while significant decreases were observed in tamoxifen and BH 10 mg/ml from 2 to 8 hr as compared with tamoxifen only, respectively. Furthermore, significant increases of Tmax in tamoxifen and BH 40 mg/ml, significant decreases of Cmax in tamoxifen and BH 20 mg/ml, significant decreases of AUC0-t, AUC0-inf and MRTinf in tamoxifen and BH 10 mg/ml were demonstrated as compared with tamoxifen only. Conclusion: Taken together, tamoxifen and BH 10 mg/ml induced significant decrease of the oral bioavailability of tamoxifen, while tamoxifen and BH 40 or 20 mg/ml did not critically influenced, suggesting formulated BH concentration-independencies. It, therefore, seems to be needed that pharmacokinetic study after repeated administration should be tested to conclude the effects of BH on the pharmacokinetics of tamoxifen.

Studies on Interaction of Tamoxifen with Sex Steroid Hormones in Rat Uterus (흰쥐의 자궁에 대한 Tamoxifen과 성스테로이드 호르몬 상호작용에 관한 연구)

  • 한호재;양일석;권종국
    • Journal of Embryo Transfer
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    • v.3 no.1
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    • pp.13-23
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    • 1988
  • These studies were undertaken to examine the interaction of tamoxifen with sex steroid hormones in rat uterine activity. The uterine wet weights of the immature Tat uterus were examined after the administration of estradiol-l7$\beta$(1$\mu$g), tamoxifen(50$\mu$g), progesterone(lmg). The uterotropic activity in immature ovariectomized rats was observed under various treatment conditions following pretreatment with above drugs. The results obtained were as follows:1) Tamoxifen produced significant increase (p <0.01) in uterine wet weight compared with control group, although the increase was not as great as that seen with estradiol-17$\beta$. Administration of estradiol-17$\beta$ together with tamoxifen inhibited significantly the increase of uterine wet weight by estradiol-17$\beta$ (p < 0.01). Coadministration of progresterone with tamoxifen partly blocked the increase of tamoxifen-induced uterine wet weights by progesterone. 2) Estradiol-17$\beta$after the estradiol-17$\beta$ pretreatment discontinued the declining uterine wet weights due to the absence of estrogen support, but uteri continued to increase in weight if daily estradiol-17 $\beta$ was maintained. Administration of tamoxifen on the fourth day of estradiol-17$\beta$ treatment reduced uterine wet weights within 24 hours, and the weights continued to decline with additional tamoxifen. 3) The modest growth of the uterus induced by three daily injections of 5Opg tamoxifen remained stable for five days, with or without additional tamoxifen treatment. Coadministration of tamoxifen with estradiol17$\beta$ increased slightly the increase of uterine wet weight by tamoxifen. Coadministration of tamoxifen with progesterone inhibited the increase of uterine wet weight by tamoxifen. 4) The modest growth of the uterus induced by three daily injections of lmg progesterone reduced uterine wet weight to the control level for five days. Commencement of tamoxifen or estadiol-17 $\beta$ injections on the fourth day of progesterone treatment rapidly elevated uterine wet weight.

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Effect of 2.5 hr-interval single oral combination treatment of Gamisoyo-san with Tamoxifen on the pharmacokinetics profiles of Tamoxifen in rats

  • Kim, Joo-Ik;Ku, Sae-Kwang;Lee, Young-Joon
    • The Journal of Korean Medicine
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    • v.41 no.4
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    • pp.1-11
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    • 2020
  • Objectives: Objectives: The object of this study was to elucidate the possible effects on the pharmacokinetics of tamoxifen after single oral co-administration of Gamisoyo-san (GMSYS) with 2.5 hr-intervals combination therapy of tamoxifen with GMSYS. Methods: After 2.5 hr of 50 mg/kg of tamoxifen treatment, GMSYS 100 mg/kg was administered. The plasma was collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMSYS treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen were analysis as compared with tamoxifen single administered rats. Results: Although single co-administration with GMSYS with 2.5 hr-interval induced increased trends of plasma tamoxifen concentrations, there are no significant changes on the plasma concentrations of tamoxifen were demonstrated in tamoxifen and GMSYS 100 mg/kg co-administrated rats with 2.5 hr-intervals as compared to those of tamoxifen single 50 mg/kg treated rats, and also GMSYS co-administrated rats did not showed any significant changes on the all pharmacokinetic parameters as compared to those of tamoxifen single formula treated rats. Conclusions: According to the this study, single co-administration of GMSYS with 2.5 hr-intervals did not critically influenced on the oral bioavailability of tamoxifen, suggesting GMSYS did not critically influenced on the absorption and excretion of tamoxifen, the oral bioavailability, when they were co-administered with 2.5 hr-intervals, at the dose levels of tamoxifen 50 mg/kg and GMSYS 100 mg/kg.

Effect of the Single Oral Combination Treatment of Tamoxifen with Gamisoyo-san on the Pharmacokinetics Profiles of Tamoxifen

  • Kim, Joo-Ik;Ku, Sae-Kwang;Lee, Young-Joon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.34 no.4
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    • pp.201-208
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    • 2020
  • The effects of Gamisoyo-san (GMSYS) co-administration within 5 min on the pharmacokinetics (PK) of tamoxifen were observed. After 50 mg/kg of tamoxifen oral treatment, GMSYS 100 mg/kg was orally administered within 5 min to 7-wk old male SPF.VAF Outbred Crl:CD [Sprague-Dawley (SD)] rats. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMSYS treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. Tmax, Cmax, AUC, t1/2 and MRTinf of tamoxifen were analysis as compared with tamoxifen single administered rats. Although co-administration with GMSYS did not critically influenced on the pharmacokinetic parameters of oral tamoxifen, they induced increased trends of plasma tamoxifen concentrations, especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 hr after end of co-administration with GMSYS as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 10 mg/kg and GMSYS 100 mg/kg within 5 min. It is considered that pharmacokinetic studies should be tested like the effects of GMSYS on the pharmacokinetics of tamoxifen, when they were co-administered with prolonger intervals than Tmax of tamoxifen oral administration (about 2.5 hr-intervals), to achieve the optimal dosing regimen of GMSYS and tamoxifen co-administration.

Tamoxifen Resistance in Breast Cancer

  • Chang, Min-Sun
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.256-267
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    • 2012
  • Tamoxifen is a central component of the treatment of estrogen receptor (ER)-positive breast cancer as a partial agonist of ER. It has been clinically used for the last 30 years and is currently available as a chemopreventive agent in women with high risk for breast cancer. The most challenging issue with tamoxifen use is the development of resistance in an initially responsive breast tumor. This review summarizes the roles of ER as the therapeutic target of tamoxifen in cancer treatment, clinical values and issues of tamoxifen use, and molecular mechanisms of tamoxifen resistance. Emerging knowledge on the molecular mechanisms of tamoxifen resistance will provide insight into the design of regimens to overcome tamoxifen resistance and discovery of novel therapeutic agents with a decreased chance of developing resistance as well as establishing more efficient treatment strategies.

Sulfasalazine attenuates tamoxifen-induced toxicity in human retinal pigment epithelial cells

  • Hwang, Narae;Chung, Su Wol
    • BMB Reports
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    • v.53 no.5
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    • pp.284-289
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    • 2020
  • Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.

Effect of Gamiondam-tang (GMODT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (2) - Single Oral Combination Treatment of Tamoxifen 50 mg/kg with GMODT 100 mg/kg with 2.5 hr-intervals -

  • Ryu, Eun-A;Kang, Su-Jin;Song, Chang-Hyun;Lee, Bong-Hyo;Choi, Seong-Hun;Han, Chang-Hyun;Lee, Young-Joon;Ku, Sae-Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.21 no.2
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    • pp.127-137
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    • 2017
  • Objectives : In our previous study, single co-administration GMODT within 5 min significantly inhibited the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Therefore, the object of this study was to elucidate the possible effects on the pharmacokinetics of tamoxifen after single oral co-administration of GMODT with 2.5 hr-intervals. Methods : After 50 mg/kg of tamoxifen treatment, GMODT 100 mg/kg was administered with 2.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMODT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen (Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats. Results : Two-half hr-interval co-administration with GMODT induced variable changes on the plasma tamoxifen concentrations as compared with tamoxifen single treated rats, and especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 (199.61%) and 1 hr (101.06%) after end of co-administration with GMODT, and also related significant (p<0.05) decreases of $t_{1/2}$ (-39.54%) and $MRT_{inf}$ (-43.94%) as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 50 mg/kg and GMODT 100 mg/kg with 2.5 hr-intervals, in this experiment. Conclusions : According to the results, GMODT critically decreased on the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Hence, the co-administration of GMODT and tamoxifen should be avoided in the comprehensive and integrative medicine, combination therapy of tamoxifen with GMODT on the breast cancer.

Effect of Jaeumkanghwatang (JEKHT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (1) - Single Oral Combination Treatment of Tamoxifen 50 mg/kg with JEKHT 100 mg/kg within 5 min -

  • Kwak, Min A;Park, Soo Jin;Park, Sung Hwan;Lee, Young Joon;Ku, Sae Kwang
    • The Journal of Korean Medicine
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    • v.37 no.2
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    • pp.1-11
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    • 2016
  • Objectives: The objective of this study was to elucidate the effect of Jaeumkanghwatang (JEKHT) on the plasma concentration and pharmacokinetics of tamoxifen in combination therapy as a process of the comprehensive and integrative medicine against breast cancer. Methods: After 50 mg/kg of tamoxifen treatment, JEKHT 100 mg/kg was orally administered within 5 min. The plasma were collected at 30 min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of JEKHT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats. Results: JEKHT did not influenced on the plasma concentrations and pharmacokinetics of tamoxifen after single oral co-administration, within 5min except for some negligible effects on plasma concentration. The $T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$ of tamoxifen in co-administered rats were quite similar to those of tamoxifen single treated rats. Conclusions: Based on the results of the present study, JEKHT did not influenced on the oral bioavailability of tamoxifen, when they were single co-administered within 5min. However, more detail pharmacokinetic studies should be tested to conclude the possibilities that can be used as comprehensive and integrative therapy with JEKHT and tamoxifen for breast cancers, when they were co-administered, like the effects on the pretreatment of JEKHT and after repeat co-administrations.

Effect of Naringin on Tamoxifen Pharmacokinetics in Rats (흰쥐에서 나란진이 타목시펜의 약물동태에 미치는 영향)

  • Kim, Hyung-Seok;Choi, Jun-Shik;Choi, In
    • Korean Journal of Clinical Pharmacy
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    • v.15 no.1
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    • pp.55-60
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    • 2005
  • The aim of this study is to investigate the effect of naringin on the pharmacokinetics of tamoxifen in rats. Tamoxifen (10 mg/kg) was administered orally 0.5 h and 3 days after oral administration of naringin (5 mg/kg). The plasma concentrations of tamoxifen were increased significantly tv naringin compared to control. Absorption rate constant ($K_a$) of tamoxifen with naringin was increased significantly compared to that of the control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations ($C_{max}$) of tamoxifen with naringin were significantly higher than those of the control. Consequently, the relative bioavailability (R.B${\%}$) of tamoxifen with naringin was 2-3-fold higher than the control, and absolute bioavailability (A.B${\%}$) of tamoxifen were significantly higher (p<0.05 with coadministration, p<0.01 with pretreatment) than those of the control. The increased bioavailability of tamoxifen in rats with naringin might be associated with the inhibition by naringin of an efflux pump P-glycoprotein and the first-pass metabolizing enzyme CYP3A4.

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Study on Antiestrogenic Effects of Tamoxifen in Immature Rat Uterus: III. Effects on Content of DNA and Protein and Uterine Wet Weight (미성숙 쥐 자궁에서 Tamoxifen의 Antiestrogen 효과에 관한 연구 : III. DNA 함량, 단백질 함량 및 자궁의 중량에 관하여)

  • Lee, Hyo-jong;Jo, Choong-ho;Park, Moo-hyun
    • Korean Journal of Veterinary Research
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    • v.27 no.1
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    • pp.9-17
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    • 1987
  • The present study has been carried out to elucidate the antiestrogenic effects of tamoxifen in immature rat uterus. The content of DNA and protein and uterine wet weight were measured after the injections of $5{\mu}g$ of estradiol-$17{\beta}$, $50{\mu}g$ of tamoxifen, a combination of both, or vehicle only subcutaneously. The results obtained were summarized as follows: 1. DNA content in uterus was increased at 48 hours after estradiol-$17{\beta}$ or tamoxifen injection (p<0.01). 2. The increament rate of uterine DNA content was significantly (p<0.01) lower in tamoxifen treated group than that in estradiol-$17{\beta}$ treated group. 3. Antiestrogenic effect of tamoxifen on protein content in uterus was apparent at 72 hours after simultaneous administration of both drugs. 4. The uterine wet weight was started to increase at three hours after the injection of estradiol-$17{\beta}$ or tamoxifen. 5. While estradiol-$17{\beta}$ increased steadily uterine wet weight up to 138.5mg at 72 hours after the injection, but tamoxifen failed to increase it after 48 hours. Tamoxifen inhibited significantly (p<0.01) the effect of estradiol-$17{\beta}$ on it thereafter.

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