• Title/Summary/Keyword: cyclosporin A

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A Strategy of Improved Formulation Development in Pharmaceutical Industry

  • Shin, Hee-Jong
    • Proceedings of the PSK Conference
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    • 2003.10a
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    • pp.44-46
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    • 2003

  • Although Cyclosporin A (CsA) is a powerful immunosuppresant with little adverse effect on the bone marrow, CsA administered orally in the general formulation cannot obtain high bioavailability due to its poor aqueous solubility. To improve the solubility and enhance the bioavailability of poorly water-soluble CsA, many different approaches have been made in our laboratory. (omitted)

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Decreased oral bioavailability of cyclosporin A at second administration in human

  • Lee, Young-Joo;Chung, Suk-Jae;Shim, Chang-Koo;Lee, Min-Wha
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.117-117
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    • 1997

  • Sandimmune Neoral$\^$(R)/ and Neoplanta$\^$(R)/ capsules were administered to twenty four healthy Korean male subjects at a cyclosporin A (CsA) dose of 175 mg in a 2 ${\times}$ 2 crossover investigation with a two-week wash-out phase. Concentrations of CsA in blood were measured by RIA method for over a period of 48 h. Result : The two formulations were found bioequivalent, but analysis of variance (ANOVA) indicated that there is a significant (p<0.01) period effect in AUC$\_$0-LAST/ (area under the blood concentration above assay limit of quantification-time curve) and C$\_$MAX/ (maximum blood concentration) between the administrations. Paired t-test revealed 6 and 9% decreases in AUC$\_$0-LAST/ and C$\_$MAX/, respectively at the second administration. This period effect on the pharmacokinetics of CsA may be relevant for the patients who need consecutive administration of the drug. A number of mechanisms, such as induction of the enzymes responsible for metabolism of the drug in the gut wall and/or liver and modulation of P-glycoprotein upon the consecutive dosing, appear consistent with the change, and needs experimental proof.

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Effect of Steroid Hormones and Intracellular $Ca^{++}$ on Taurine Transporter Activity in Murine Macrophage Cell Line (마우스 대식세포에서 스테로이드 호르몬과 세포내 $Ca^{++}$ 타우린수송체의 활성에 미치는 영향)

  • 김하원;안혜숙;이선민;이은진;현진원;박건구;박태선;김병각
    • Biomolecules & Therapeutics
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    • v.9 no.1
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    • pp.40-45
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    • 2001

  • The activity of taurine transporter is affected by various extracellular stimuli such as ion, hormone and stress. To assess effects of steroid hormones antral cyclosporin A (CsA) on the taurine transporter activity, murine monocytic RAW264.7 cell line was stimulated with dexamethasone (DM), triamcinolone (TA), cortisone (CS), hydrocortisone (HCS), prednisone (PSN), prednisolone (PSL) and methylprednisolone (MPSL) in the presence of 12-0-tetradecanoylphorbol-13-acetate(TPA). Treatment of TPA on the cell line led to significant reduction of taurine transporter activity. However, in case of stimulation of the cells with steroid hormones in the presence of TPA, all of them recovered TPA-induced reduction of the taurine transporter activity. Treatment of the cells with CsA led to significant reduction of the taurine transporter activity. Ionomycin (IM) recovered the reduced taurine transporter activity by CsA, but failed in the presence of EDTA, a calcium chelating agent. These results showed that glucocorticoid hormone recovered TPA-induced reduction of taurine transporter activity and that IM recovered CsA-induced reduction of the transporter activity by increasing intracellular free $Ca^{++}$ concentration.n.

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Heterologous Expression of Novel Cytochrome P450 Hydroxylase Genes from Sebekia benihana

  • Park Nam-Sil;Park Hyun-Joo;Han Kyu-Boem;Kim Eung-Soo
    • Journal of Microbiology and Biotechnology
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    • v.16 no.2
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    • pp.295-298
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    • 2006

  • Actinomycetes are ubiquitous Gram-positive soil bacteria and a group of the most important industrial microorganisms for the biosynthesis of many valuable secondary metabolites as well as the source of various bioconversion enzymes. Cytochrome P450 hydroxylase (CYP), a hemebinding protein, is known to be involved in the modification of various natural compounds, including polyketides, fatty acids, steroids, and some aromatic compounds. Previously, six different novel CYP genes were isolated from a rare actinomycetes called Sebekia benihana, and they were completely sequenced, revealing significant amino acid similarities to previously known CYP genes involved in Streptomyces secondary metabolism. In the present study, these six CYP genes were functionally expressed in Streptomyces lividans, using an $ermE^{*}$ promoter-containing Streptomyces expression vector. Among six CYP genes, two S. benihana CYP genes (CYP503 and CYP504) showed strong hydroxylation activities toward 7-ethoxycoumarin. Furthermore, the recombinant S. lividans containing both the S. benihana CYP506-ferredoxin genes as well as the S. coelicolor feredoxin reductase gene also demonstrated cyclosporin A hydroxylation activity, suggesting potential application of actinomycetes CYPs for the biocatalysts of natural product bioconversion.

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