• Title/Summary/Keyword: dicarboxylate

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Hepatotoxicity in treatment of canine dermatophytosis with ketoconazole (피부사상균 감염개에서 Ketoconazole 경구투여시의 간독성에 관한 연구)

  • Bae, Seong-su;Kim, Cheol-ho;Kim, Tae-yung;Kang, Chung-boo
    • Korean Journal of Veterinary Research
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    • v.45 no.2
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    • pp.255-261
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    • 2005
  • The purpose of this study is to compare hepatotoxicity of each treatment for dermatophytosis; one is the administration of the ketoconazole only and the other, ketoconazole with diphenyl-dimeththyl-dicarboxylate. Have chosen the range of 14-24 months of healthy dogs divided by two groups (group 1 and group 2) for the experiment of which test proved positive in dermatophytosis diagnosis and showed normal reaction in terms of physical examination, blood chemistry and especially of liver function. Group 1 was administrated ketoconazole orally at 10 mg/kg/day and of same dose of ketoconazole with diphenyl-dimethyl-dicarboxylate for group 2. After administering, we have tested two groups by blood collecting every one week in order to check the differences of hepatotoxicity state through AST, ALT and r-GTP, the barometers of liver function which lasted for 12 weeks. Moreover, tested Indocyanine Green (ICG), known as susceptible gauge of function of excretion before starting the experiment and tested ICG as well after 12 weeks. The experiment of result the value of group 1 in AST, ALT and r-GTP has been highly rised after administering ketoconazole for 10 weeks meanwhile, of group 2 has shown a steady state troughout the whole experiment. For ICG test, we injected 0.5 mg/kg of ICG into a vein for both groups and tested the retention rate at regular interval of 15, 30, 45 minutes. The results of retention rate in two groups were similar to before the drug administration. However, after 12 weeks the retention rate of group 1 has been delayed, on the other hand, retention rate of group 2 were a steady state. In conclusion, the administration of ketoconazole only for a long period of time induced hepatotoxicity where as, the administration of ketoconazole with diphenyl-dimethyl-dicarboxylate didn't induce hepatotoxicity. Therefore, when doctors prescribes for a dog with dermatophytosis should not administrate ketoconnazole itself but with diphenyl-dimethyl-dicarboxylate and one who has abnormal condition of liver function should not be prescribed ketoconazole treatment. If there is a case needed to prescribe ketoconazole treatment, the regular monitoring should be accompanied by at the same time.

Formulation Optimization of the Tablet Prepared with Solid Dispersion of Biphenyl Dimethyl Dicarboxylate with Poloxamer (비페닐 디메칠 디카르복실레이트 고체분산체 정제 처방의 최적화)

  • Lee, Jang-Won;Park, Eun-Seok;Chi, Sang-Cheol
    • Journal of Pharmaceutical Investigation
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    • v.28 no.4
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    • pp.267-274
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    • 1998
  • Biphenyl dimethyl dicarboxylate (DDB) has been used for the treatment of acute and chronic hepatitis. However, its poor solubility in water, $2.5\;{\mu}g/ml$, caused low bioavailability of the drug after its oral administration. In order to increase the dissolution of DDB in gastrointestinal tracts, consequently to increase the bioavailability of the drug, DDB tablet was prepared with solid dispersion of DDB with poloxamer 338 or 407 using a direct compression method. To improve the flowability of the solid dispersion, Aerosil was used as an adsorbent. The effect of formulation variables (poloxamer and Aerosil contents) on the dissolution rate of DDB from tablets was investigated using an analysis of variance. The dissolution rate of DDB from tablets was evaluated with KP II (paddle) method. The dissolution patterns of the drug from the tablet prepared with poloxamer 407 were affected significantly by the contents of poloxamers and Aerosil over the range employed, but those of the drug from the tablet prepared with poloxamer 338 were not. The optimum formulation of the DDB tablet, showed the same dissolution pattern as that of the reference, was obtained after polynomial equations of drug dissolution profiles for each formula were fitted to contour plots. The optimum formulation ratios of DDB:poloxamer 407:Aerosil were 1:2.5:2.5 and 1:5:5.

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Bioequivalence Test of Biphenyl Dimethyl Dicarboxylate Products (비페닐디메칠디카르복실레이트 제제의 생물학적 동등성 시험)

  • Han, Sang-Soo;Ham, Seong-Ho;Sohn, Dong-Hwan;Kim, Jae-Baek
    • Journal of Pharmaceutical Investigation
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    • v.24 no.2
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    • pp.67-72
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    • 1994
  • Bioequivalence (BE) test of biphenyl dimethyl dicarboxylate (DDB) tablets was performed. Normal healthy male volunteers (n = 20) were randomly divided into 2 groups, and reference $(Nissel{\circledR})$ and test $(Livital{\circledR})$ tablets of DDB $(25mg{\times}8\;Tab.\;= \;200\;mg)$ were given orally by balanced two-period cross-over design. The serum concentration was determined by high performance liquid chromatography. The pharmacokinetic parameters, AUC, $C_{max}$, and $T_{max}$ obtained after drug administration were statistically analyzed. Statistical evaluation of the data involved an analysis of variance (ANOVA) for cross-over design. The results were within 20% differences of mean value in AUC, $C_{max}$, and $T_{max}$ between reference and test tablets. The results of ANOVA showed no significant differences for "between group or subject" and "period". The test tablet was bioequivalent with the reference tablet in the AUC, $C_{max}$, and $T_{max}$.

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New Synthetic Route to 1, 4-Dihydropyridine Monoacid Derivatives (1, 4-디히드로피리딘산 유도체의 새로운 제조방법에 관한 연구)

  • Shim, Young-Key;Lee, Sang-Hee;Kang, Jae-Sung;Kim, Wan-Joo
    • Journal of the Korean Chemical Society
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    • v.32 no.2
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    • pp.144-148
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    • 1988
  • A novel synthetic route to 1,4-dihydropyridine mono carboxylic acid derivatives is described. Allyl methyl 2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylate (IV) was treated with $Pd(OAc)_2$ in dioxane for 30 min at 110$^{\circ}C$ with reflux to give the mono acid compound(V) in 94% yield. The mono acid intermediate was converted to 2-(N-benzyl-N-methylamino)ethyl methyl 2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3, 5-dicarboxylate (VII) (Nicardipine) and their derivatives in 70~85% yield.

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Structure and Properties of Polynorbornene Derivatives: Poly(norbornene dicarboxylic acid dialkyl ester)s and Poly(norbornene dimethyl dicarboxylate)s

  • Shin, Boo-Gyo;Cho, Tai-Yon;Yoon, Do-Y.;Liu, Binyuan
    • Macromolecular Research
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    • v.15 no.2
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    • pp.185-190
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    • 2007
  • Poly(norbornene dimethyl dicarboxylate)s, (PNDMD)s, were prepared by addition polymerization with palladium(II) catalyst from pure exo-monomers, and their structure and properties were compared with those of poly(norbornene dicarboxylic acid dialkyl ester)s, (PNDADA)s. Both polymer series exhibited good solubility in general organic solvents and excellent thermal stability up to $330^{\circ}C$. Wide-angle X-ray scattering (WAXS) study indicated the presence of nano-scale layer-like order in amorphous PNDADAs, while PNDMDs showed random amorphous structure. The glass transition temperatures and dielectric constants of solid polymers were found to decrease as the alkyl side-chain length increases for both polymer series. However, PNDMDs showed lower glass transition temperatures and higher dielectric constants, as compared with those of PNDADAs containing the same alkyl substituents. This difference, caused by the higher side-group mobility of PNDMDs, may be closely related to the nano-scale order in amorphous PNDADAs and its absence in PNDMDs.

Syntheses, Crystal Structures, and Spectral Properties of Two Coordination Compounds Based on 1,2-Bis(benzimidazolyl)benzene

  • Meng, Fa-Yan;Jiang, Bing-Li;Lin, Cui-Wu;Wang, Li;Tan, Xiao-He
    • Bulletin of the Korean Chemical Society
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    • v.32 no.3
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    • pp.1017-1021
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    • 2011
  • Two new benzimidazolyl-containing complexes have been synthesized by reactions of $Cu^{II}$ salts and 1,2-bis(benzimidazolyl) benzene ($H_2bbbz$) with two different dicarboxylate ligands. When phthalate acid ($H_2pt$) was employed as secondary ligand, a 0D molecular complex Cu$(H_2bbbz)(pt){\cdot}(H_2pt)$ (1)was furnished and when the secondary ligand was instead by a linear bridging ligand of terephthalic acid ($H_2tp$) a 1D zipper-like coordination polymer $[Cu(H_2bbbz)(tp){\cdot}2(C_2H_5OH){\cdot}H_2O]_n$ (2) was obtained, suggesting the structure-direction effect of the secondary dicarbxylate ligand. The preliminary investigation on the spectral properties of the complexes was also presented.