Studies on the metabolic fate of nizatidine. (I). Absorption, distribution, metabolism and excretion after a single administration to rats.

Sano, Hiroshi; Satō, Hiroshi; Toyama, Seiji; Tagashira, Eijiro; ESUMI, Yoshio; Katami, Yoshiharu; Tohjo, Hideaki; Yatsu, Sachiko; Yokoshima, Tetsuyoshi

doi:10.2133/dmpk.4.31

Cited by 7 publications

(10 citation statements)

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“…At this dosage regimen, the maximum blood level of MK-4 is 1 mmol/L (36). In a distribution study in rats, MK-4 distribution in the liver was at least 10 times greater than that in plasma after oral administration (37). This liver MK-4 level is comparable with the IC 50 values of MKH-DMG for HCC growth inhibition.…”

Section: Inhibition Of Hcc Cell Growth By Mkh-dmgmentioning

confidence: 52%

Enhanced Antitumor Effects of Novel Intracellular Delivery of an Active Form of Menaquinone-4, Menahydroquinone-4, into Hepatocellular Carcinoma

Setoguchi

Watase

Matsunaga

et al. 2015

Cancer Prevention Research

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Reduced cellular uptake of menaquinone-4 (MK-4), a vitamin K 2 homolog, in human hepatocellular carcinoma (HCC) limits its usefulness as a safe long-term antitumor agent for recurrent HCC and produces des-g-carboxy prothrombin (DCP). We hypothesized that effective delivery of menahydroquinone-4 (MKH), the active form of MK-4 for g-glutamyl carboxylation, into HCC cells is critical for regulating HCC growth, and may enable it to be applied as a safe antitumor agent. In this study, we verified this hypothesis using menahydroquinone-4 1,4-bis-N,N-dimethylglycinate hydrochloride (MKH-DMG), a prodrug of MKH, and demonstrated its effectiveness. Intracellular delivery of MKH and subsequent growth inhibition of PLC/PRF/5 and Hep3B (DCPpositive) and SK-Hep-1 (DCP-negative) cells after MKH-DMG administration were determined and compared with MK-4. The activity of MKH-DMG against tumor progression in the liver alongside DCP formation was determined in a spleen-liver metastasis mouse model. MKH-DMG exhibited greater intracellular delivery of MKH in vitro (AUC 0-72 hour of MKH) and increased growth-inhibitory activity against both DCP-positive and DCP-negative HCC cell lines. The phenomena of MKH delivery into cells in parallel with simultaneous growth inhibition suggested that MKH is the active form for growth inhibition of HCC cells. Cell-cycle arrest was determined to be involved in the growth inhibition mechanisms of MKH-DMG. Furthermore, MKH-DMG showed significant inhibition of tumor progression in the liver, and a substantial decrease in plasma DCP levels in the spleen-liver metastasis mouse model. Our results suggest that MKH-DMG is a promising new candidate antitumor agent for safe long-term treatment of HCC. Cancer Prev Res; 8(2); 129-38.Ó2014 AACR.

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Section: Inhibition Of Hcc Cell Growth By Mkh-dmgmentioning

confidence: 52%

Enhanced Antitumor Effects of Novel Intracellular Delivery of an Active Form of Menaquinone-4, Menahydroquinone-4, into Hepatocellular Carcinoma

Setoguchi

Watase

Matsunaga

et al. 2015

Cancer Prevention Research

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“…Polaprezinc, a synthetic agent, N-(3-aminopropionyl)-Lhistidinate zinc, is a chelate compound developed for ulcer healing [16,17]. Zinc contained in orally administered polaprezinc is absorbed, however, and leads to a rise in serum concentrations of zinc [18]. In this respect, absorption of polaprezinc is more favorable than other zinccontaining derivatives, such as zinc sulfate.…”

Section: Discussionmentioning

confidence: 99%

Blood cell, liver function, and response changes by PEG-interferon-α2b plus ribavirin with polaprezinc therapy in patients with chronic hepatitis C

Kim

Sasase

et al. 2008

Hepatol Int

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Purpose Zinc has been reported to ameliorate hematologic side effects and improve liver function. In addition to its various effects, zinc supplementation in chronic hepatitis C patients with genotype 1b of high viral load enhanced the response to interferon (IFN) monotherapy. This study was aimed at clarifying whether zinc could improve hematologic side effects, improve liver function, and enhance the response to therapy in patients with chronic hepatitis C treated with pegylated-interferon (PEG-IFN) plus ribavirin (RBV). Methods The 32 patients enrolled in the study were randomly divided into two groups: a PEG-IFN-a2b plus RBV with zinc group (PEG/RBV + zinc, n = 16) and a PEG-IFN-a2b plus RBV group (PEG/RBV, n = 16). HCV-RNA, serum zinc, ALT, white blood cell, red blood cell, platelet, and hemoglobin (Hb) levels were examined. Results Serum zinc levels were significantly higher in the PEG/RBV with zinc group than in the PEG/RBV without zinc group at 4, 8, and 12 weeks. No significant differences were observed in the clearance of HCV-RNA between the two groups. The outcome of the treatment was similar; results of laboratory examinations including ALT before, during, and after therapy revealed no significant differences between the two groups at any point in all items except serum zinc levels. A sustained virological response rate was observed in 50.0% in the PEG/RBV with zinc group and 43.8% in the PEG/RBV without zinc group, with no significant difference between the two groups. Conclusions The study demonstrated no evidence that zinc ameliorates hematologic side effects, improves liver function, and enhances the response to the therapy in chronic hepatitis C receiving PEG-IFN-a2b plus RBV.

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Section: Discussionmentioning

confidence: 99%

“…Zinc present in the orally administered polaprezinc is absorbed, leading to a rise in serum concentration of zinc [21] . In this respect, absorption of polaprezinc is more favorable than other zinc-containing derivatives such as zinc sulfate [21] . While the dose of polaprezinc could increase serum zinc concentration and possibly improve the SVR, caution should be exercised with regard to the side effects of higher doses of polaprezinc, as it is known to induce abdominal discomfort in some patients (personal communication).…”

Section: Discussionmentioning

confidence: 99%

Triple therapy of interferon and ribavirin with zinc supplementation for patients with chronic hepatitis C: A randomized controlled clinical trial

Suzuki

Takagi²,

Sohara³

et al. 2006

WJG

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AIM:To study the therapeutic effect of interferon (IFN) and ribavirin with zinc supplement on patients with chronic hepatitis C viral (HCV) infection. M E T H O D S :A t o t a l o f 1 0 2 p a t i e n t s c o n f i r m e d histologically to have chronic HCV infection with genotype 1b and more than 100 KIU/mL of HCV were randomly assigned to each arm of the study and each received 10 million units of pegylated interferon (IFNalpha-2b) daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin (600 or 800 mg/d depending on body weight), with or without polaprezinc (150 mg/d) orally for 24 wk. The primary endpoint was sustained virological response (SVR) defined as negative HCV-RNA in the serum 6 mo after treatment. RESULTS:There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group (P < 0.05). SVR was observed in 33.3% of the triple therapy group and 33.3% of the dual therapy group. The side effects were almost the same in both groups except for gastrointestinal symptoms, which were less in the triple therapy group (P = 0.019).CONCLUSION: Considered together, triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype 1b and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects.

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Studies on the metabolic fate of nizatidine. (I). Absorption, distribution, metabolism and excretion after a single administration to rats.

Cited by 7 publications

References 0 publications

Enhanced Antitumor Effects of Novel Intracellular Delivery of an Active Form of Menaquinone-4, Menahydroquinone-4, into Hepatocellular Carcinoma

Enhanced Antitumor Effects of Novel Intracellular Delivery of an Active Form of Menaquinone-4, Menahydroquinone-4, into Hepatocellular Carcinoma

Blood cell, liver function, and response changes by PEG-interferon-α2b plus ribavirin with polaprezinc therapy in patients with chronic hepatitis C

Triple therapy of interferon and ribavirin with zinc supplementation for patients with chronic hepatitis C: A randomized controlled clinical trial

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