• Asian-Australasian Journal of Animal Sciences
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• v.14 no.2
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• pp.276-279
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• 2001

The effect of helminthiasis on zinc metabolism was monitored using endogenous $^{65}Zn$ after intraperitoneal injection of 1 g of $^{65}Zn$ as zinc chloride. In the first experiment zinc turnover was investigated in 18 male weanling rats, which were randomly divided into 3 groups. One group was infected with 73 third stage larvae of Nippostrongylus brasiliensis per gram body weight ; the other groups were the pair-fed and ad lib-fed controls. The route of loss of zinc was investigated in the second experiment with the same design using 18 animals with a lower dose of infection (33 larvae per gram body weight). The biological half life of endogenous $^{65}Zn$ was lower (p<0.05) in the infected group as compared to the controls. In the later phase of infection (9th to 16th day) there was reduced retention of $^{65}Zn$ and increased loss (p<0.05) of $^{65}Zn$ from the body though urine and faeces. It was concluded that infection of N. brasiliensis was accompanied by increased loss of endogenous Zn through faeces and urine.

• Journal of Pharmaceutical Investigation
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• v.6 no.2
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• pp.88-94
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• 1976

This paper attempted to investigate the effect of pretreatment with carbon tetrachloride on absorption, excretion, protein binding, and biological half-life of sulfisoxazol from rats and rabbits. Absorption of sulfisoxazol was found to decrease in severe damage rats, compared with that of normal rats, but in mild rats, absorption of sulfisoxazol was similar to that of nomal rats. Absorption of sulfisoxazol was decreased significantly in severe damage rabbit pretreated with carbon tetrachloride but in mild damage rabbit, absorption of sulfisoxazol was not influenced significantly. Pretreatment with carbon tetrachloride gave the effect on clearance of sulfisoxazol in part but protein binding percent of sulfisoxazol was not influenced by concentration of carbon tetrachloride.

• Journal of Pharmaceutical Investigation
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• v.13 no.4
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• pp.173-182
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• 1983

The influence of prazosin (0.1 mg/kg i.v.) on the excretion and diuretic action of furosemide (2mg/kg i.v.) in rabbits was studied to investigate an interaction between ${\alpha}-adrenergic$ blocking agent, prazosin and furosemide. The results were as follows; 1) With the combined administration of prazosin and furosemide, the plasma concentration of furosemide was increased, the urinary excretion rate and renal clearance of furosemide were reduced, and tile biological half-life of furosemide was increased. 2) The diuretic action of furosemide was significantly reduced with the combined administration of prazosin: maximal decrease in urine volume, urinary electrolytes, clearance of $Na^+$ and $Cl^-$, and GFR and RPF, as well as maximal increase in $Na^+$ reabsorption rate were noted 10 minutes after administration of furosemide (2mg/kg i.v.)

• YAKHAK HOEJI
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• v.25 no.3
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• pp.101-108
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• 1981

Quantitative determination of capsaicin in biological fluid was investigated. The pharmacokinetic study of capsaicin in rabbits was performed by high-pressure liquid chromatography, equipped with a microparticulate reversed-phase column and a fixed wavelength detector. Elution was carried out using methanolwater(70:30). It allows the quantitative determination at 8-400 ng level. When single dose of capsaicin(4mg/kg) was given to rabbits intravenously, the elimination phase was extremely short with average half-life to 17.35 minute. Urine excretion of capsaicin itself during first 2 hours after intravenous administration (4mg/kg) was 0.004-0.04% of the administered amount. The maximum plasma concentration of capsaicin after oral administration (300mg/kg) was $4{\times}10^{-7}$g/ml at 40 minutes. The $LD_{50}$ of capsaicin in mouse was 0.40mg/kg (i.v.) and 47.2 mg/kg (p.o.) which was determined by Litchfield and Wilcoxon's method, suggesting that the gastrointestinal absorption of capsaicin is poor.

• YAKHAK HOEJI
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• v.29 no.6
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• pp.362-366
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• 1985

These paper was attempted to investigate the mechanism of increased blood level of sulfisomidine by cimetidine pretreatment pharmacokinetically. Especially, effect of cimetidine pretreatment on both renal clearance and biliary clearance of sulfisomidine was studied in rabbits. The results are as follows. The blood level of sulfisomidine administered intravenously in dose of 25mg/kg was elevated significantly by cimetidine pretreatment. Relative bioavailability and biological half-life were increased significantly by cimetidine pretreatment. Overall elimination rate constant ($betha$) and distribution rate constant ($K_{13}$) of sulfisomidine were decreased significantly by cimetidine pretreatment. The renal and biliary clearance of sulfisomidine were decreased significantly compared with those of control rabbits by cimetidine pretreatment. The results may be also related to the inhibition of sulfisomidine metabolism enzyme activity or reduction of blood flow in the liver.

• Korean Journal of Clinical Pharmacy
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• v.3 no.1
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• pp.1-13
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• 1993

The intraction between cimetidine and rifampicin was studied pharmacokinetically in normal human subjects. The serum level and the area under the serum concentration curve(AUC) of rifampicin administrated orally were elevated significantly by cimetidine. Volume of distribution, total clearance and elimination rate constant of rifampicin were reduced significanyly by cimetidine. Biological half-life of rifampicin was prolonged significantly by cimetidine. The mechanism of this results is probably related to the inhibition of rifampicin metabolism(deacetyl form) or reduction of blood flow in the liver. It is desirable that dosage regimen of rifampicin shoud be adjusted when combined with cimetidine in clinical pharmacy practice.

• YAKHAK HOEJI
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• v.27 no.2
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• pp.149-154
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• 1983

The effect of hydrochlorothiazide on the pharmacokinetics of carteolol in rabbits was studied. Animals were divided into two groups (group I and group II). Group I received carteolol (12mg/kg) and group II received carteolol (12mg/kg) with hydrochlorothiazide (20mg/kg) orally. The carteolol concentration in serum was measured by spectrofluorometric method and its pharmacokinetic parameter values were calculated. The serum concentration of carteolol in group II was significantly increased when compared with those in group I at 10min (p<0.01), and at 30min (p<0.05) after p. o. administration. In addition, the absorption rate constant of carteolol in group II was slightly increased and Tmax of carteolol in group II was significantly shortened (p<0.05) and Cmax of carteolol in group II was significantly increased (p<0.02) when compared with those in group I. But elimination rate constant and biological half-life of carteolol were similar in both groups.

• YAKHAK HOEJI
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• v.32 no.5
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• pp.319-327
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• 1988

Pharmacokinetic interaction of cimetidine and isoniazid was investigated in the rabbits. Isoniazid was administered orally at a dose of 30mg/kg to six rabbits after 10, 20, and 30mg/kg pretreatment of cimetidine twice a day for 10days. Concentration of the free and the total isoniazid in the blood and the urine was determined by spectrophotometer. Relative bioavailability and biological half-life($t\frac{1}{2}{\beta}$) were increased significantly by cimetidine pretreatment. Overall elimination rate constant and total clearance of isoniazid were decreased significantly by cimetidine pretreatment. The ratio of metabolites to isoniazid in the blood and the urine was decreased significantly by cimetidine pretreatment. Relative bioavailability, INAH to metabolites ratio in the blood and decrease in total clearance were highly correlated with the does of cimetidine pretreated. This result might be due to the inhibition of isoniazid metabolism in the liver by cimetidine pretreatment.

• Journal of Pharmaceutical Investigation
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• v.30 no.2
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• pp.73-83
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• 2000

Polyethylene glycol (PEG) is a water soluble, biocompatible, non-toxic polymer and PEGylation is a well established technique for the modification of therapeutic proteins and peptides. PEG-protein drugs have been extensively studies in relation to therapies for various diseases: cancer, inflammation and others. The covalent attachment of PEG to proteins and peptides prolonged plasma half-life, reduced antigenicity and immunogenicity, increased thermal and mechanical stability, and prevented degradation by enzymes. Several chemical groups for general and site specific conjugation have been exploited to activate PEG for amino group, carboxyl group, and cysteine groups. PEGylation of many proteins and peptides have been studied to enhance their properties for the potential uses. Also, the different positional isomers in several PEG-proteins have shown the difference in vivo stability and biological indicating that the site of PEG molecule attachment is one of the important factor to develop PEG-proteins as potential therapeutic agents.

• Animal cells and systems
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• v.4 no.2
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• pp.157-163
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• 2000

Yeast pheromone a-factor is a 13-amino acid peptide hormone that is synthesized as a part of a larger precursor, prepro-$\alpha$-factor, consisting of a signal peptide and a proregion of 64 amino acids. The carboxy-terminal half of the precursor contains four tandem copies of mature $\alpha$-factor. To investigate the molecular basis of intracellular sorting, proteolytic processing, and storage of the peptide hormone, yeast prepro-$\alpha$-factor precursors were heterologously expressed in rat pituitary $GH_3 cells. When cells harboring the precursor were metabolically labeled, a species of approximately 27 kD appeared inside the cells. Digestion with peptide: N-glycosidase F (PNG-F) shifted the molecular mass to a 19 kD, suggesting that the 27 kD protein was the glycosylated form as in yeast cells. The nascent polypeptide is efficiently targeted to the ER in the $GH_3 cells, where it undergoes cleavage of its signal peptide and core glycosylation to generate glycosylated pro-a-factor. To look at the post ER intracellular processing, the pulse-labelled cells were chased up to 2 hrs. The nascent propeptides disappeared from the cells at a half life of 30 min and only 10-25% of the newly synthesized, unprocessed precursors were stored intracellularly after the 2 h chase. However, about 20% of the pulse-labeled pro-$\alpha$-factor precursors were secreted into the medium in the pro-hormone form. With increasing chase time, the intracellular level of propeptide decreased, but the amount of secreted propeptide could not account for the disappearance of intracellular propeptide completely. This disappearance was insensitive to lysosomotropic agents, but was inhibited at $16^{circ}C or 20^{\circ}C$, suggesting that the turnover of the precursors was not occurring in the secretory pathway to trans Golgi network (TGN) or dependent on acidic compartments. From these results, it is concluded that a pan of these heterologous precursors may be processed at its paired dibasic sites by prohormone processing enzymes located in TGN/secretpry vesicles producing small peptides, and that the residual unprocessed precursors may be secreted into the medium rather than degraded intracellularly.