• Journal of fish pathology
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• v.23 no.3
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• pp.357-367
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• 2010

The pharmacokinetic properties of amoxicillin trihydrate (Amox) were studied after single oral administration and single intravenous injection to cultured eel, Anguilla japonica, respectively (average $220{\pm}10\;g$, $28{\pm}1^{\circ}C$). Plasma samples were taken at 3, 5, 10, 15, 24, 30, 48, 96 and 144 h post-dose. The kinetic profile of absorption, distribution and elimination of Amox in plasma were analyzed fitting to a two-compartment model by WinNonlin program. In oral dosage of 40 and 80 mg/kg body weight, the peak plasma concentrations of Amox, which attained at 3~12 h post-dose, were 3.4 and $3.3\;{\mu}g/ml$, respectively. In intravenous injection with 1 mg/kg, the peak plasma concentrations of Amox, which attained at 9 h post-dose, was $7.2\;{\mu}g/ml$. The following parmeters were calculated for a single oral dosage of 40 and 80 mg/kg body weight, respectively: AUC (the area under the concentration-time curve)= 464 and $667\;{\mu}g{\cdot}h/ml$; $T_{max}$ (time for maximum concentration)= 2.1 and 3.6 h; $C_{max}$ (maximum concentration)= 3.04 and $3.4\;{\mu}g/ml$. Following intravenous injection at 1 mg/kg, this parameters were AUC= $748\;{\mu}g{\cdot}h/ml$; $C_{max}=4.2\;{\mu}g/ml$. The apparent oral bioavailability at 40 and 80 mg/kg were 1.6 and 1.1%, respectively. Despite using the trihydrate form of amoxicillin, the oral bioavailability was low in eel.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.15 no.2
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• pp.160-167
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• 2004

Objectives : There have been very few studies on the compliance of methylphenidate-immediate releasing form(MPH-IR), which is the most frequently used drug in Korea, in Attention Deficit Hyperactivity Disorder(ADHD). This study was conducted to investigate the compliance rate and the related factors in the one year pharmacotherapy process via OPD for children with ADHD. Method : Total 100 ADHD patients were selected randomly among patients who have been treated with MPH-IR from September in 2002 to December in 2002. All the selected patients were diagnosed with DSM-IV-ADHD criteria and fulfilled the inclusion criteria. In March, 2003(at the time of 6 month treatment), all the patients and parents received the questionnaire for the compliance and satisfaction for MPH-IR treatment. In October 2003(at time of 1 year treatment), we, investigators evaluated the socio-demographic variables, developmental data, medical data, family data, comorbid disorders, treatment variables, and compliance rate. Through these very comprehensive data, The compliance rate at the time of mean 1 year treatment and the related factors were investigated. Result : 1) In the questionnaire for compliance and satisfaction for MPND treatment, the 60% of respondents(parents) reported more than moderate degree of satisfaction in the effectiveness of MPND. Their compliance rate for the morning prescription was 81%, but the rate of afternoon prescription was 43%. 2) In the evaluation at the time of 1 year treatment(October 2003), the 38% of parents were dropped out from the OPD treatment. The mean compliance rate for the 1 year treatment was 62%. the 38% of parents were dropped out from the OPD treatment. The mean compliance rate for the 1year treatment was 62%. 3) Compared with the noncompliant group(drop-out group), compliant group showed higher total, verbal and performance IQ scores. In the treatment variables, higher reposponder rate(clinician rating), higher medication dosage and more compliance rate in afternoon prescription were found in the compliant group compared with the noncompliant group. There were no statistical differences in the demographic variables(age, sex, SES, parental education level), medical data, developmental profiles and academic function. Conclusion : To our knowledge, this is the first report about the compliance rate of the MPH-IR treatment for the children with ADHD. The compliance rate at the time of mean 1year treatment was 62%, which was comparable with other studies performed in foreign countries, especially States. In this study, the compliance related factors were IQ score, clinical treatment response, dosage of MPH-IR, and early compliance for the afternoon prescription. These results suggest that clinician plan the strategies for the promotion of the early compliance for the after prescription and enhancement of overall treatment response.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.280-285
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• 1996

The sustained release dosage form which delivers melatonin (MT) in a circadian fashion over 8 h is of clinical value for those who have disordered circadian rhythms because of its short halflife. The purpose of this study was to evaluate the gelling properties and release characteristics of alginate beads varying multivalent cationic species $(Al^{+++}, \; Ba^{++}, \; Ca^{++}, \; Mg^{++}, \; Fe^{+++}, \; Zn^{++})$. The surface morphologies of Ca- and Ba-alginate beads were also studied using scanning electron microscope (SEM). MT, an indole amide pineal hormone was used as a model drug. The $Ca^{++}, \; Ba^{++}, \; Zn^{++}, \; Al^{++}\; and\; Fe^{+++}\; ions\; except\; Mg^{++}$ induced gelling of sodium alginate. The strength of multivalent cationic alginate beads was as follows: $Al^{+++}\llFe^{+++} the induced hydrogel beads were very fragile and less spherical. Fe-alginate beads were also fragile but stronger compared to Al-alginate beads. Ba-alginate beads had a similar gelling strength but was less spherical when compared to Ca-alginate beads. Zn-alginate beads were weaker than Ca- and Ba-alginate beads. Very crude and rough crystals of Ba- and Ca-alginate beads at higher magnifications were observed. However, the type and shape of rough crystals of Ba- and Ca-alginate beads were quite different. No significant differences in release profiles from MT-loaded multivalent cationic alginate beads were observed in the gastric fluid. Most drugs were continuously released upto 80% for 5 h, mainly governed by the passive diffusion without swelling and disintegrating the alginate beads. In the intestinal fluid, there was a significant difference iq the release profiles of MT-loaded multivalent cationic alginate beads. The release rate of Ca-alginate beads was faster when compared to other multivalent cationic alginate beads and was completed for 3 h. Ba-alginate beads had a very long lag time (7 h) and then rapidly released thereafter. MT was continuously released from Feand Zn-alginate beads with initial burstout release. It is assumed that the different release rofiles of multivalent cationic alginate beads resulted from forces of swelling and disintegration of alginate beads in addition to passive diffusion, depending on types of multivalent ions, gelling strength and drug solubility. It was estimated that 0.2M $CaCl_2$ concentration was optimal in terms of trapping efficiency of MT and gelling strength of Ca-alginate beads. In the gastric fluid, Ca-alginate beads gelled at 0.2 M $CaCl_2$ concentration had higher bead strength, resulting in the most retarded release when compared to other concentrations. In the intestinal fluid, the decreased release of Ca-alginate beads prepared at 0.2 M $CaCl_2$ concentration was also observed. However, release profiles of Ca-alginate beads were quite similar regardless of $CaCl_2$ concentration. Either too low or high $CaCl_2$ concentrations may not be useful for gelling and curing of alginate beads. Optimal $CaCl_2$ concentrations must be decided in terms of trapping efficiency and release and profiles of drug followed by curing time and gelling strength of alginate beads.

• Journal of the korean academy of Pediatric Dentistry
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• v.24 no.1
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• pp.27-40
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• 1997

This study investigated the effects of laser irradiation on the exposed pulp and the possibility of direct pulp capping with the $CO_2$ laser. Results were obtained from the observation of the residual pulpal healing process. Class V cavities on 48 anterior teeth from 8 adult dogs were prepared and pulp chambers were intentionally opened with dental explorer. The control group consisted of 16 teeth. $Dycal^{(R)}$(Caulk Co., U.S.A.) was applied to exposed site once bleeding was stopped. Cavities were sealed with $I.R.M^{(R)}$. In the experimental group 1 (16 teeth), laser(LASERSAT $CO_2^{(R)}$, Satelec Co.) was irradiated on the exposed pulp. The laser procedure followed the manufacturers recommendations for the treatment of human pulp(1.5 Watts, 0.2 seconds, unfocused), and cavities were sealed with $I.R.M^{(R)}$. In the experimental group 2 (16 teeth), laser was irradiated on the exposed pulp in a more powerful dosage(5.0 Watts, 0.2 seconds, unfocused), and cavities were sealed with $I.R.M^{(R)}$. Two dogs were sacrificed immediately after experiment and the others were sacrificed at intervals of one, three, and eight weeks respectively. All teeth were routinely processed and the pulpal tissues and odontoblastic layers were observed by the light microscope. The results were as follows; 1. In the control group, the initial mild inflammation had improved to normal by week eight. An active formation of reparative dentin was observed at week three, and at week eight, a firm dentin bridge was present beneath the $Dycal^{(R)}$ with no inflammatory responses in the remaining pulp. 2. In the experimental group 1, immediately following irradiation, the superficial shape of the exposed pulp was crater-like. And it was lined with the coagulated layer, $60{\sim}70{\mu}m$ in width. Moderate inflammatory pulpal conditions existing at week one were improved to mild at week eight. And from the week three specimens, a reparative dentin formation was observed in the adjacent odontoblastic layer of the exposed site. A dentin bridge at the exposed site, however, did not form during the experimental period. 3. In the experimental group 2, the width of the coagulation layer lining the crater was $70{\sim}130{\mu}m$. Beneath the coagulated layer, severe inflammatory pulpal responses were observed at week one, and conditions did not improve during the experimental period.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.469-476
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• 2010

This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration ($C_{max}$) of oral paclitaxel. Apigenin significantly increased the terminal half-life ($t_{1/2}$, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.

• The Korean Journal of Food And Nutrition
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• v.15 no.4
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• pp.364-369
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• 2002

Streptomyces shows a eukaryotic characteristic that vegetative cell can grow into mycelial form and has morphological and physiological differentiation at a certain period during its life cycle. Streptomyces has been used for the production of many biologically active compounds, such as antibiotics and pronase. Production of second metabolites and differentiation of the vegetative cell share the certain period of its lift cycle. Therefore, second metabolites may affect the differentiation of the vegetative cell. One of the microbial hormone, called A-factor, regulates the production of second metabolites, sporulation and differentiation of the cells. Streptomyces griseus produces streptomycin as well as many different kinds of proteinase. As mentioned, period of proteinases production overlaps with the period of differentiation of the vegetative cells. Protease may play a important role for the differentiation of the cells. In this paper, function of the SGPD gene cloned from S. griseus IFO 13350 tested whether it affects for the differentiation of A-factor mutated S. griseus HH1 and S. griseus IFO13350. pWHM3 and pWHM3-sprD plasmid was transformed into S. griseus HH1 and S. griseus IFO13350. Chymotrypsin activity of the cultured medium of the transformants with pWHM3-sprD plasmid didn't show any change with that of the transformants with plasmid only. The transformants with pWHM3-sprD plasmid didn't show the increase of the production of actinorhodin as well as morphological change in S. griseus IFO 13350 and HH1, as well. The promoter sequences of the SGPA and SGPB gene which encode chymotrypsin-like protease, were compared with that of SGPD gene. Regulatory mechanism of gene expression of proteinase genes will be studied for the development of high production system for protease as well as the function of the proteases.

• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.71-82
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• 1996

This study has been undertaken to evaluate hydrophobic cyclodextrin(CD) derivatives as a sustained release carrier of azidothymidine(AZT), AZT, which has potent activity against AIDS and AIDS-related complex as thymidine analogue, has been reported that it has significant toxicity and short half life. Therefore, it is necessary to design sustained release oral dosage form to avoid undesirable side effects attributable to an excessive plasma concentration and to reduce the frequency of administration of AZT. Inclusion complexes of AZT with $acetyl-{\beta}-cyclodextrin\;(AC{\beta}CD)$ and $triacetyl-{\beta}-cyclodextrin(TA{\beta}CD)$ were prepared by solvent evaporation method. Interactions of AZT with CD were investigated by Differential Scanning Calorimetry(DSC) and Infrared Spectrophotometry(IR). The decreasing order of water solubilities of AZT and AZT-CD inclusion complexes were as follows; $AZT\;(27.873{\pm}0.015,mg/ml)\;>\;AZT-AC{\beta}CD\;(3.377{\pm}0.003)\;>\;AZT-TA{\beta}CD\;(2.528{\pm}0.001)$. Partition coefficients of $AZT-AC{\beta}CD\;and;\AZT-TA{\beta}CD$ inclusion complexes were increased by 1.27-fold, 1.54-fold in pH 1.2 and 1.32-fold, 1.47-fold in pH 6.8 in comparison with that of AZT. The mean dissolution time (MDT, min) which represents the rapidity of dissolution rate of AZT, $AZT-AC{\beta}CD,\;AZT-TA{\beta}CD$ were 5.12, 14.02 and 19.38 min in pH 1.2 and 2.52, 15.19 and 18.19 min in pH 6.8. AZT was very rapidly and completely dissolved in pH 1.2 and pH 6.8 within 5 minutes. But AZT-CD inclusion complexes showed the sustained release pattern in comparison with AZT alone. The simultaneous in situ nasal and jejunal recirculation study to compare the intrinsic absorptivity and the property of absorption sites revealed that the absorption of $AZT-TA{\beta}CD\;(N:35.35{\pm}1.08%,\;J:27.47{\pm}1.18%)$ was more than that of $AZT\;(N:16.89{\pm}2.25%,\;J:15.86{\pm}2.33%)$. The above results suggest that $TA{\beta}CD$ which is a hydrophobic cyclodextrin may serve as sustained release carrier with absorption enhancing effect.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.185-190
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• 2002

To improve the solubility of poorly water-soluble drug and to develop a sustained release tablets, the need for the technique, the formation of solid dispersion with polymeric materials that can potentially enhance the dissolution rate and extent of drug absorption was considered in this study. The 1:1, 1:4, and 1:5 solid dispersions were prepared by spray drying method using PVP K30, ethanol and methylene chloride. The dissolution test was carried out at in phosphate buffer solution at $37^{\circ}C$ in 100 rpm. Solid dispersed drugs were examined using differential scanning calorimetry and scanning electron microscopy, wherein it was found that felodipine is amorphous in the PVP K30 solid dispersion. Felodifine SR tablets were prepared by direct compressing the powder mixture composed of solid dispersed felodipine, lactose, Eudragit and magnesium stearate using a single punch press. In order to develop a sustained-release preparation containing solid dispersed felodipine, a comparative dissolution study was done using commercially existing product as control. The dissolution rate of intact felodipine, solid dispersed felodipine and its physical mixture, respectively, were compared by the dissolution rates for 30 minutes. The dissolution rates of felodipine for 30 minutes from 1:1, 1:4, 1:5 PVP K30 solid dispersion were 70%, 78% and 90%. However, dissolution rate offelodipine from the physical mixture was 5% of drug for 30 minutes. Our developed product Felodipine SR Tablet showed dissolution of 17%, 50% and 89% for 1, 4, and 7 hours. This designed oral delivery system is easy to manufacture, and drug releases behavior is highly reproducible and offers advantages over the existing commercial product. The dissolution rate of felodipine was significantly enhanced, following the formation of solid dispersion. The solid dispersion technique with water-soluble polymer could be used to develop a solid dispersed felodipine SR tablet.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.4
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• pp.538-545
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• 2017

Objective: The goal of this study was to investigate the effects of cupric citrate (CuCit) on growth performance, antioxidant indices, serum lipid metabolites, serum immune indices, and tissue residues of copper (Cu), zinc, and iron in weaned pigs. Methods: A total of 180 weaned pigs ($Duroc{\times}Landrace{\times}Large$ White) with an average body weight of $8.98{\pm}1.21kg$ were randomly assigned to a corn-soybean meal control ration, or 4 similar rations with 30, 60, 120, or 240 mg/kg Cu as CuCit. All diets contained 10 mg/kg Cu as cupric sulfate from the vitamin-mineral premix. The experiment was divided into two phases: 0 to 14 d (phase 1) and 15 to 28 d (phase 2). Results: Average daily gain (ADG; linearly, p<0.01) and average daily feed intake (ADFI; linearly and quadratically, p<0.05) were affected by an increase in CuCit during phase 2. Overall period, ADG (p<0.05) and ADFI (p<0.01) were linearly increased with increasing dietary levels of CuCit. Serum malondialdehyde concentrations (p<0.05) and glutathione peroxidase activity (p<0.01) linearly decreased and increased respectively with an increase in CuCit. Serum levels of Cu-Zn superoxide dismutase were linearly affected with an increase in CuCit (p<0.01). Hepatic malondialdehyde levels decreased with an increase in CuCit (linearly and quadratically, p<0.01). Serum total cholesterol concentrations were quadratically affected (p<0.05) and decreased in pigs fed Cu as CuCit at 60 and 120 mg/kg and increased in pigs fed 240 mg/kg Cu as CuCit. Serum high-density lipoprotein concentrations were linearly affected with an increase in CuCit (p<0.01). Serum $IL-1{\beta}$ levels were quadratically affected (p<0.05) by dietary treatment. Compared with other treatments, 240 mg/kg Cu from CuCit quadratically increased hepatic (p<0.01) and renal (p<0.05) Cu concentrations, and quadratically decreased hepatic and renal iron concentrations (p<0.05). Conclusion: Cu administered in the form of CuCit at a dosage range of 30 to 60 mg/kg, effectively enhanced the growth performance and antioxidant status of weaned pigs.

• The Journal of Churna Manual Medicine for Spine and Nerves
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• v.10 no.1
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• pp.117-127
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• 2015

Objectives : Most of pains are important symptoms caused by cancer transpered to spine. Harpagophyti Radix Pharmacopuncture is highly effective in reducing fever, pain, inflammation but was never used to reduce pain from cancer transpered to spine. So I intended to use Harpagophyti Radix Pharmacopuncture to control pain. The purpose of this study is to evaluate the clinical application of Harpagophyti Radix Pharmacopuncture for Bone Metastasis of Breast Cancer and Spinal Stenosis. Methods : We examined patient with Bone Metastasis of Breast Cancer and Spinal Stenosis who admitted Jaseng Korean Medicine Hospital. The patient was treated by Korean Medicine treatment and Harpagophyti Radix Pharmacopuncture. This case was assessed by Numerical Rating Scale(NRS), Oswestry Low Back Pain Disability Index(ODI), Short-Form 36 Health Survey(SF-36), ROM(Range of Movement) and Special Test. Results : In this study, the patient's pain was controlled and NRS, ODI were decreased. I could identify the improvement in life quality from the positive change of SF-36 and also found out that treatment was successful from the improvement of ROM, Special test. Conclusions : Harpagophyti Radix Pharmacopuncture with Korean Medicine treatment for Bone Metastasis of Breast Cancer and Spinal Stenosis was proved to be useful to the pain relief and function recovery, but further research should take place for clear understanding of the exact amount of dosage and safety. Moreover it must be accompanied by long term follow up research.