• YAKHAK HOEJI
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• v.44 no.5
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• pp.424-431
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• 2000

A biopharmaceutics drug classification system for correlation between in vitro dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling the rate and extent of drug absorption. The objective of this study was to assess whether in vitro dissolution profiles of immediate-release beta-blocker tablets can be correlated with intestinal membrane permeability and/or in vivo bioavailability In vitro dissolution of the beta-blocker tablets was examined using KP VII Apparatus II methods at various pH. Intestinal membrane permeability was determined in vitro using the diffusion chamber method. Bioavailablity parameters were cited from literatures. The dissolution profiles did not accurately represent the in vivo bioavailablity However there were good correlations between intestinal membrane permeability and log P (noctanol/buffer). The correlations obtained in this study indicated that in vitro diffusion chamber method could be used to predict intestinal absorption in vivo.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.275-282
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• 1998

In order to develop a desirable in vitro release which correlates well with in vivo bioavailability, hollow type suppository containing Propranolol HCl(PPH) powder in the cavity and conventional type suppository with dispersed PPH in the base were prepared. Polyvinyl alcohol (PVA) hydrogel as a base and PPH as a model drug were used for the preparation of suppository. The rates of drug release from the suppositories were studied by Paddle method, Muranish method, Dialysis tubing method and Rotating dialysis cell method. The release profiles from suppositories using the four different release tests were compared. After a rectal administration in rat, the mean $C_{max}$ of hollow type suppository was significantly lower than that of conventional type, but $T_{max}$, $AUC_{0{\to}12}$ and MRT of hollow type were significantly higher 1.6 times, 1.2 times and 1.9 times than those of conventional type, respectively. The computer program was used to simulate plasma concentration from in vitro released amounts of drug and in vivo pharmacokinetic parameters. Based on comparison of the simulated bioavailability from computer program with experimental bioavailability in rat we have found out in vitro release test which correlates well with in vivo bioavailability. Our results have shown the best correlation between in vitro release and in vivo bioavailability in PPH-PVA hydrogel hollow type suppository for the paddle method and conventional type suppository for the rotating dialysis cell method. In this work we propose that PPH-PVA hydrogel suppository shows in vitro-in vivo correlation. This data should help to optimize the formulation of the drug and provide a basis for quality control procedures.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.89-94
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• 2003

In vivo clearance of BMS-182874 was primarily due to metabolism via stepwise N-demethylation. Despite in vivo clearance approached ca 50％ of the total liver plasma flow, BMS-182874 was completely bioavailable after oral administration in rats. Saturable first-pass metabolism and the role of extrahepatic tissue were evaluated as possible reasons for complete oral bioavailability despite extensive metabolic clearance. Pharmacokinetic parameters were obtained after an intravenous and a range of oral doses of BMS-182874 in rats. Bile and urine were collected from bile-duct cannulated (BDC) rats and the in vivo metabolic pathways of BMS-182874 were evaluated. Pharmacokinetics of BMS-182874 were also compared in nephrectomized (renally impaired) vs. sham-operated control rats. Oral bioavailability of BMS-182874 averaged 100％, indicating that BMS-182874 was completely absorbed and the first-pass metabolism (liver or intestine) was negligible. The AUC and C/sub max/ values increased dose-proportionally, indicating kinetics were linear within the oral dose range of 13 to 290 mmole/kg. After intravenous administration of BMS-182874 to BDC rats, about 2％ of intact BMS-182874 was recovered in excreta, indicating that BMS-182874 was cleared primarily via metabolism in vivo. The major metabolite circulating in plasma was the mono-N-desmethyl metabolite and the major metabolite recovered in excreta was the di-N-desmethyl metabolite. In vivo clearance of BMS-182874 was significantly reduced in nephrectomized rats. These observations suggest saturable first-pass metabolism is unlikely to be a mechanism for complete oral bioavailability of BMS-182874. Reduced clearance observed in the nephrectomized rats suggests that extrahepatic tissues (e.g., kidneys) may play an important role in the in vivo clearance of xenobiotics that are metabolized via N-demethylation.

• Journal of Pharmaceutical Investigation
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• v.17 no.3
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• pp.127-133
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• 1987

Dissolution characteristics and urinary excreted amount of commercially available three brands of sulfisoxazole tablets were investigated in order to elucidate the in vitro-in vivo correlations and relative bioavailability in humans. All the tablets tested met the K.P. IV and the USP XXI specifications for tablet weight variation, content uniformity, disintegration and dissolution. The disintegration and dissolution rate constants of sulfisoxazole tablets in pH 2.0 HCl-KCl buffer were reduced more significantly (p<0.05) than those in diluted HCl $(1{\rightarrow}12.5)$ and pH 6.5 phosphate buffer. It seemed to be attributed to the pH dependent solubility of sulfisoxazole. We could see that the relative bioavailability of brand B to sulfisoxazole powder was about 90% and that its value was higher than those of other two brands from the urinary excretion data obtained from eight healthy male volunteers by means of Latin square cross over design. No useful correlation was observed between the in vitro and in vivo studies in this experiment.

• Nutritional Sciences
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• v.3 no.2
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• pp.71-76
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• 2000

Effects of extrusion processing on zinc bioavailability in a product made from 85% semolina and 15% soy protein concentrate were determined using in vitro and in vivo techniques. Soluble and dialyzable zinc contents of the extruded product were 15.3 and 13.0 $\mu$g/g, respectively, compared to 15.6 to 15.0$\mu$g/g in the raw (unprocessed) ingredients. Zinc bioavailability in diets in which all of the zinc (14ppm) was provided either by the extruded product or by its raw ingredients was determined in two groups of male Sprague Dawley rats. No differences were found in concentrations of zinc in plasma, liver and femur between rats fed the two experimental diets. Apparent zinc digestibility was similar for both diets. These results are consistent with the in vitro results showing no effect of extrusion processing on zinc bioavailability.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.272-277
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• 1997

The effect of nonionic surfactant(polyoxyl 40 hydrogenated castor oil, PHCO), a common solubi-lizer, on the solubility of silymarin in the combined preparation containing ursoseoxycholic acid(UDCA) and silymarin was investigated in vivo using HPLC. The solubility of silybin, a major component of silymarin, was enhanced by increasing the amount of PHCO. The effect of PHCO on bioavailability was also evaluated in rats. The bioavailability was calculated by silybin content in bile juice that was excreted for 24 hr after oral administration. It was found that the bioavailability of silymarin containing PHCO was significantly increased compared to that of control. These results suggest that PHCO may improve the solubility and bioavailabilty of silymarin when it is combined with UDCA and silymarin.

• International Journal of Advanced Culture Technology
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• v.6 no.4
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• pp.109-115
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• 2018

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.

• YAKHAK HOEJI
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• v.47 no.5
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• pp.331-338
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• 2003

A butyrolactone ester of cefazolin (CFZ-BTL) was synthesized by the esterification of cefazolin (CFZ) with $\alpha$-bromo-${\gamma}$-butyrolactone. The synthesis was confirmed by the spectroscopic analysis. The CFZ-BTL was more lipophilic than the CFZ when assessed by n-octanol/water partition coefficients at various pH. The CFZ-BTL itself did not show any antimicrobial activity in vitro, but after oral administration of CFZ-BTL to rabbits, exerted significant anti-microbial activity in serum samples when measured by the inhibion zone method in nutrient agar plates, due to conversion of CFZ-BTL to an active metabolite, probably CFZ, in the body. The CFZ-BTL was also converted into CFZ as confirmed by in vitro incubation study, with tissue homogenates (liver, blood and intestine) of rabbits. The liver showed the fastest conversion rate, probably via the hydrolysis mechanism. In vivo metabolism of CFZ-BTL to CFZ was also confirmed in vivo serum samples by HPLC. The oral bioavailability of CFZ-BTL in rabbits was 1.6-fold increased when compared to CFZ, resulting from followed by enhanced lipophilicity increased passive absorption in the intestine.

• YAKHAK HOEJI
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• v.31 no.5
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• pp.286-295
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• 1987

The relationship between in vitro release and in vivo bioavailability of acetaminophen from suppositories was investigated. Effect of glycyrrhizin on the drug release and rectal absorption in rats was also examined. Suppositories containing 25mg of acetaminophen were prepared with Wecobee FS (fatty base) or PEG (water-soluble base) bases. The release from the suppositories were determined with USP rotating basket dissolution apparatus and with the suppository release tester. The temperature of the dissolution medium was very critical for the dissolution of acetaminophen from Wecobee FS suppositories. The bioavailability of acetaminophen was calculated from the plasma concentration-time curve after rectal administration of the suppositories to the rats. There were no significant differences in AUC following rectal administration of Wecobee FS and PEG suppositories, but the release and absorption from the Wecobee FS suppositories were faster than those from PEG suppositories. The dissolution rate obtained by the suppository release tester was better correlated with in vivo absorption rate constant than that by the USP dissolution apparatus. It suggests that the partitioning between rectal fluid and suppository base is the rate-limiting step in the rectal absorption of acetaminophen from suppositories. Glycyrrhizin was found not to affect in vitro dissolution and rectal absorption of acetaminophen.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.419.2-420
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• 2002

Caco-2 is a cell line derived from the human colon adenocarcinoma and often used as a model for studying intestinal drug absorption. It has been well-known that a strong correlation holds between in vitro permeability across Caco-2 cell monolayers and in vivo bioavailability for various drugs. but the correlation curves varied depending on laboratories. The permeabilities of drugs across Caco-2 cell monolayers have been measured under different agitation conditions. (omitted)