• Journal of Pharmaceutical Investigation
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• v.35 no.1
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• pp.1-5
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• 2005

ABSTRACT -Ipriflavone is a synthetic flavonoid derivate that improves osteoblast cell activity inhibiting bone resorption. In order to improve the bioavailability, solid dispersions of ipriflavone with PVP (poly-N-vinylpyrrolidone, MW=40,000 g/mole) were prepared by a spray-drying method. During the manufacturing of solid dispersion, various solvents [ethanol (EtOH), acetonitrile, methylene chloride and cosolvent-EtOH:acetone=1:1] were used to dissolve the ipriflavone and PVP. Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were used to evaluate the physicochemical interaction between ipriflavone and PVP. Particle size, crystallinity and the area of the endotherm $({\Delta}H)$ of solid dispersed ipriflavone using the acetonitrile as solvent were much smaller than those of the other preparation types. Bioavailability of ipriflavone in vivo was changed by solvents. When considering the result of in vivo test, solid dispersion of ipriflavone using the acetonitrile as solvent showed the best choice.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.275-284
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• 2024

Worldwide, cardiovascular disease is the main cause of death, which accordingly increased by hyperlipidemia. Hyperlipidemia therapy can include lifestyle changes and medications to control cholesterol levels. Statins are the medications of the first choice for dealing with lipid abnormalities. Rosuvastatin founds to control high lipid levels by hindering liver production of cholesterol and to achieve the targeted levels of low-density lipoprotein cholesterol, another lipid lowering agents named ezetimibe may be used as an added therapy. Both rosuvastatin and ezetimibe have low bioavailability which will stand as barrier to decrease cholesterol levels, because of such depictions, formulations of this combined therapy in nanotechnology will be of a great assistance. Our study demonstrated preparations of nanoparticles of this combined therapy, showing their physical characterizations, and examined their behavior in laboratory conditions and vivo habitation. The mean particle size was uniform, polydispersity index and zeta potential of formulations were found to be in the ranges of (0.181-0.72) and (-13.4 to -6.24), respectively. Acceptable limits of entrapment efficiency were affirmed with appearance of spherical and uniform nanoparticles. In vitro testing showed a sustained release of drug exceeded 90% over 24 h. In vivo study revealed an enhanced dissolution and bioavailability from loaded nanoparticles, which was evidenced by calculated pharmacokinetic parameters using triton for hyperlipidemia induction. Stability studies were performed and assured that the formulations are kept the same up to one month. Therefore, nano formulations is a suitable transporter for combined therapy of rosuvastatin and ezetimibe with improvement in their dissolution and bioavailability.

• YAKHAK HOEJI
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• v.44 no.6
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• pp.528-533
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• 2000

This study was to develop an effective itraconazole liquid preparation which exhibits an enhanced bioavailability. The solubility of itraconazole was increased (72-fold) in itraconazole liquid preparation as compared with itraconazole powder. The dissolution rate of itraconazole was higher for itraconazole liquid preparation filled into a hard gelatin capsule with 90% release within 20 min as compared to 55% for $Sporanox^{\circledR}$capsules. The oral absorption of itraconazole liquid preparation and $Sporanox^{\circledR}$tablets were studied in the rat. The area under the concentration-time curve $(AUC_{0-24hr})$ of itraconazole liquid preparation ($90.25\;{\pm}\;8.36\;{\mu}g{\cdot}hr/ml$) increased by 6.2 times compared to that of Sporanox tablets ($14.58\;{\pm}\;1.26\;{\mu}g{\cdot}hr/ml$) after oral administration of itraconazole 15 mg/rat each. $C_{max}$ also increased to $6.87\;{\pm}\;1.15\;{\mu}g/ml$ after administration of liquid preparation $1.58\;{\pm}\;0.16\;{\mu}g/ml$ of $Sporanox^{\circledR}$tablets. These results indicate that in vivo bioavailability of itraconazole liquid preparation was significantly enhanced as compared with $Sporanox^{\circledR}$tablets.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.173-179
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• 2002

Solid dispersions of ipriflavone with PVP were prepared by a spray-drying method in order to improve the bioavailability. They were measured with scanning electron microscopy, differential scanning calorimetry, x-ray powder diffraction, and Fourier transform infrared spectroscopy to evaluate the physicochemical interaction between ipriflavone and PVP and study the correlation between these physicochemical characteristics and bioavailability. Ipriflavone exhibited crystallinity, whereas PVP was almost amorphous. The area of the endotherm $({\Delta}H)$ of freezer milled ipriflavone, freezer milled ipriflavone physically mixed with freezer milled PVP, and physically mixed ipriflavone with PVP was almost the same, whereas ${\Delta}H$ of the solid dispersed ipriflavone with PVP was much smaller than that of the other preparation types. Also, the crystallinity and the crystal size of ipriflavone in the solid dispersed ipriflavone with PVP were much smaller than those of the other preparation types. From the in vivo test, the AUC of the solid dispersed ipriflavone with PVP was approximately 10 times higher than that of the physically mixed ipriflavone with PVP. The solid dispersion using the spray-drying method with a water-soluble polymer, PVP, may be effective for the improvement of the bioavailability.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.304.1-304.1
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• 2001

• Biomedical Science Letters
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• v.24 no.3
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• pp.280-284
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• 2018

The incidence of cardiovascular diseases (CVDs) is increasing rapidly in developed countries, with CVDs now representing the leading cause of morbidity and mortality. Natural products and ethnomedicines have been shown to reduce the risk of CVDs. Garlic is a medicinal plant used throughout the world for its anti-inflammatory, antioxidant, and antiplatelet activities. Chitosan is a natural polysaccharide obtained from chitin, and derivatives of chitosan have been shown to inhibit platelet aggregation and adhesion. We hypothesized that fermented preparations of these products may possess stronger antiplatelet effects than the non-fermented forms owing to the increased bioavailability of the bioactive compounds produced during fermentation. Therefore, we compared these compounds via in vitro and ex vivo platelet aggregation assays by using standard light transmission aggregometry and ex vivo granule secretions from rat platelets. We found that fermented preparations exerted more potent and significant inhibition of platelet aggregation both in vitro and ex vivo. Likewise, ATP release from dense granules of platelets was also significantly inhibited in fermented preparation-treated rat platelets compared to that in non-fermented preparation-treated ones. We concluded that fermented preparations exerted more potent effects on platelet function both in vitro and ex vivo, possibly as a result of the increased bioavailability of active compounds produced during fermentation. We therefore suggest that fermented products may be potent therapeutics against platelet-related CVDs and can be used as antiplatelet and antithrombotic agents.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.446-452
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• 2016

Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.334-343
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• 2021

Background: Gut microbiota mainly function in the biotransformation of primary ginsenosides into bioactive metabolites. Herein, we investigated the effects of three prebiotic fibers by targeting gut microbiota on the metabolism of ginsenoside Rb1 in vivo. Methods: Sprague Dawley rats were administered with ginsenoside Rb1 after a two-week prebiotic intervention of fructooligosaccharide, galactooligosaccharide, and fibersol-2, respectively. Pharmacokinetic analysis of ginsenoside Rb1 and its metabolites was performed, whilst the microbial composition and metabolic function of gut microbiota were examined by 16S rRNA gene amplicon and metagenomic shotgun sequencing. Results: The results showed that peak plasma concentration and area under concentration time curve of ginsenoside Rb1 and its intermediate metabolites, ginsenoside Rd, F2, and compound K (CK), in the prebiotic intervention groups were increased at various degrees compared with those in the control group. Gut microbiota dramatically responded to the prebiotic treatment at both taxonomical and functional levels. The abundance of Prevotella, which possesses potential function to hydrolyze ginsenoside Rb1 into CK, was significantly elevated in the three prebiotic groups (P < 0.05). The gut metagenomic analysis also revealed the functional gene enrichment for terpenoid/polyketide metabolism, glycolysis, gluconeogenesis, propanoate metabolism, etc. Conclusion: These findings imply that prebiotics may selectively promote the proliferation of certain bacterial stains with glycoside hydrolysis capacity, thereby, subsequently improving the biotransformation and bioavailability of primary ginsenosides in vivo.

• Journal of Pharmaceutical Investigation
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• v.27 no.2
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• pp.125-131
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• 1997

Ethoxycarbonyloxyethyl ester of ceftezole (CFZ-ET) was synthesized as a prodrug by esterification of ceftezole (CFZ) with ethoxycarbonyloxyethyl chloride and was confirmed by spectroscopic analyses. CFZ-ET was more lipophillic than CFZ as assessed by n-octanol and water partition coefficients at various pH. CFZ-ET itself did not show any microbiological activity in vitro, but showed substaintial microbiological activity after oral administration of CFZ-ET, indicating that CFZ-ET is converted to microbiologically active metabolite, probably CFZ, in the body. When CFZ-ET was incubated in blood, liver and intestine homogenates of rabbits, liver homogenate showed the fastest conversion of CFZ-ET. CFZ-ET appears rapidly metabolized in the liver when given orally due to the hydrolysis of the ester to CFZ, the parent drug of CFZ-ET. In vivo metabolism of CFZ-ET to CFZ was confirmed in rabbit by HPLC analysis. CFZ-ET were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-ET was 1.5-fold higher than that of CFZ in rabbits because of enhanced lipophilicity and absorption. Based on these findings, CFZ-ET appears useful as a prodrug of CFZ to improve the oral bioavailability of CFZ.

• YAKHAK HOEJI
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• v.33 no.4
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• pp.229-236
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• 1989

Even though two different preparations are chemically equivalent, the variance of bioavailability differenciates the clinical effect of preparations, so that the preparations need to be evaluated by comparing bioavailability in vivo as well as chemical equivalence. In this study, bioequivalence tests of commercially available isoniazid tablets A, B, C and D (standard) were performed to give some guidelines to bioequivalence test. The bioavailability parameters obtained by drug administeration were statistically analyzed. Statistical evaluation of the data involved an analysis of variance for a cross over design. Cross over design was employed with 8 healthy volunteers. The results were within 20% difference of mean value in the AUC, Cmax, Tmax and amount of urinary excretion (Au) between standard and isoniazid tablets. The results of ANOVA showed no significant differences for 'group or sequence', but almost not for 'between subjects'. The tablet. A, B and D were within 20 min, but tablet C was within 50 min. Tablet A was biologically equivalent in the Au. tablet B biologically equivalent in the Au and AUC. Tablet C was biologically equivalent in the Au. The relationship between the dissolution rate and Au was significant.