• Archives of Pharmacal Research
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• v.10 no.3
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• pp.184-187
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• 1987

ln order to develope anti-inflammatory glucocorticoids for local use without systemic side-effects, ester and amide derivatives of 20$\xi$-dihydroprednisolonic acid have been prepared. When binding affinities of these compounds to glucocorticoid receptor of rat liver cytosol were compared, all a-isomer at C-20 showed higher binding affinities than the corres¬ponding $\beta$-isomer. The size of the substituents at C-21 had significant influences on binding affinities, which were related with their lipophilicity.

• Journal of Pharmaceutical Investigation
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• v.35 no.2
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• pp.111-116
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• 2005

The unstirred water layer (UWL), which has been known to exist in the boundary of the intestinal lumen and intestinal wall, often behaves as an absorption barrier especially for lipophilic drugs. The intestinal absorption of drugs is often characterized using Caco-2 cell monolayers grown on Transwell polycarbonate membranes. The permeability $(P_{app})$ of drugs across the cell monolayer might be influenced by the agitation of the donor compartment, since the width of UWL on the surface of the cell monolayer would be reduced by the agitation. In this study, the effect of agitation of the donor compartment with 60 rpm on the permeability was measured for 12 drugs with a wide range of lipophilicity and permeability. The $P_{app}$ of mannitol, tributylmethyl ammonium, cimetidine, ranitidine, hydrocortisone, benzylpenicillin and loxoprofen was not influenced by the agitation, while the $P_{app}$ of theophylline, propranolol, YH439, phenylpropanolamine and testosterone was increased by the agitation. There was a significant correlation between the increase of $P_{app}$ by agitation and the lipophilicity for the compounds having $P_{app}>2{\times}10^{-5}$ cm/sec. No correlation was observed for the difference in $P_{app}$ by agitation and the molecular weight, or lipophilicity of the drugs. Therefore, the agitation rate of the donor compartment in the Caco-2 cell monolayer study should be carefully controlled in order to estimate $P_{app}$ reproducibly especially for lipophilic drugs.

• Journal of Pharmaceutical Investigation
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• v.35 no.2
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• pp.71-74
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• 2005

The aim of this study was to analyze characteristics of the barrier function of excised porcine buccal mucosa to the test compounds, estradiol, propranolol HCI, melatonin, and mannitol with a wide range of partition coefficient values. The permeability of melatonin was measured through frozen, stored, and fresh porcine buccal mucosa to examine the impact of storage conditions on the permeability of porcine buccal mucosa. The results demonstrated that the ex vivo permeability of the porcine buccal mucosa was greater for more lipophilic solutes, which was consistent with a series of molecules transported by passive transepithelial diffusion. The melatonin permeation profiles through frozen, stored, and fresh mucosa illustrated that damage was incurred by the freezing process of the mucosal tissue, leading to loss of the barrier function and thereby an increased permeation coefficient. It can be observed that the influence of compound lipophilicity on the association of the compounds with buccal mucosa was clear. The relationship between permeation coefficient and Log P values for the four compounds investigated demonstrated a proportional relationship, further confirming the importance of the lipophilicity of a compound to permeate the buccal mucosa. These results showed that the ex vivo porcine buccal mucosa model is a suitable tool to screen oral mucosal permeability.

• Archives of Pharmacal Research
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• v.26 no.10
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• pp.778-784
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• 2003

N'-(1-alkyl-2,3-dihydro-2-oxo-1H-3-indolyliden)-4-pyridinecarboxylic acid hydrazide derivatives, 3(a-g), were synthesized in a trial to overcome the resistance developed with the therapeutic uses of isoniazid (INH). The lipophilicity of the synthesized derivatives supersedes that of the INH as expressed by Clog p values. The synthesized compounds and INH were tested against bovin, human sensitive and human resist strains of Mycobacterium tuberculosis. Compounds 3a, 3d, 3f and 3g with 1-unsubstituted, 1-propyl, 1-propynyl and 1-benzyl groups respectively exhibited equipotent growth inhibitory activity (MIC 10 $\mu$mol) against the tested strains as compared with INH however the later has no activity against human resist strain. Pharmacokinetic study revealed that the rate and extent of absorption of the tested derivatives (3d and 3f) significantly higher than that of INH (p＜0.05). The relative bioavailabilities ($F_R%$) were 183.15 and 443.25 for 3f and 3d respectively as compared to INH. These results preliminary indicate the possible use of the prepared derivatives for treatment of tuberculosis infections in order to overcome the resistance developed with INH.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.133-138
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• 1998

Phthalimidyl ester of ceftezole (CFZ-PT) was synthesized as a prodrug by esterification of ceftezole (CFZ) with N-bromophthalimide. CFZ-PT was more lipophilic than CFZ when the lipophilicity was assessed by partition coefficients between n-octanol and water at various pH. The pharmacokinetic characteristic of CFZ-PT and CFZ preparations were compared following oral administrations of these compounds to rabbits. CFZ-PT is expected to be metabolized rapidly to CFZ in the body. The metabolism process appears to be hydrolysis of the ester to CFZ, the parent drug of CFZ-PT. In vivo metabolism of CFZ-PT to CFZ was confirmed in rabbit by HPLC analysis. CFZ concentration in the serum samples taken after oral administration of CFZ-PT(equivalent amount of CFZ) were released and higher than those of CFZ. Oral bioavailability of CFZ-PT was 1.9 fold higher than at of CFZ in rabbits because of enhanced lipophilicity and absorption. Finally, it was concluded that CFZ-PT appears useful as a prodrug of CFZ to improve the oral bioavailability of CFZ.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.130-130
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• 2002

Polychlorinated biphenyls (PCBs) are persistent environmental contaminants that elicit a broad spectrum of toxic effects in mammals and other vertebrate species. Because of their lipophilicity, chemical stability and resistance to biodegradation, PCBs tend to accumulate in the human body via food chain and environmental matrices including human adipose tissues, blood and milk.(omitted)

• YAKHAK HOEJI
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• v.30 no.2
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• pp.68-72
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• 1986

Effect of sodium taurodeoxycholate (TDC) on the pharmacokinetics of methylene blue (MB) was investigated in the rats of experimental hepatic failure induced by $CCI_4$. Intravenous infusion of TDC increased the distribution volume of central compartment ($Vd_1$) and the total body clearance ($CL_t$) of MB. Increased lipophilicity through ion-pair formation with TDC seemed to be the probable cause of increased $Vd_1$ and $CL_t$.

• The Korean Journal of Nuclear Medicine
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• v.26 no.1
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• pp.133-139
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• 1992

To improve the quality of $^{99m}Tc-methylenediphonate$ $(^{99m}Tc-MDP)$ for skeletal imaging, different composed $^{99m}Tc-MDP$ complexes were prepared with addition of antioxidants such as ascorbic acid, getisic acid, and p-aminobenzoic acid. To characterize the different $^{99m}Tc-MDP$ preparations, some physical and biochemical properties of $^{99m}Tc-MDP$ such as thermal stability, lipophilicity and bindability to serum protein were studied and organ distribution pattern of these complexes also compared. The thermal stabilities of $^{99m}Tc-MDP$ contained antioxidants were dependant mainly on pH, temperature, and elapsed time after the preparation. $^{99m}Tc-MDP$ complex contained gentisic acid as antioxidant was extremely unstable at alkaline condition. The most stable $^{99m}Tc-MDP$ was found in the presence of p-aminobenzoic acid. $^{99m}Tc-MDP$ complexes with antioxidants were very lipophilic but lipophilicity differences in antioxidants were not observed. The bindability of $^{99m}Tc-MDP$ to serum protein was not affect at pH $5.0\sim9.0$ by the different antioxidants. However, protein binding percentage of $^{99m}Tc-MDP$ with ascorbic acid was relatively low (22.7%) at pH 9.0. In biodistribution studies in mice, bone to muscle ratios of $^{99m}Tc-MDP$ preparations containing ascorbic acid, gentisic acid, and p-aminobenzoic acid were 15.3, 24.5, and 30.1, respectively. Im to our results, p-aminobenzoic acid is fond to be the most promising antioxidant.

• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.313-319
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• 2002

Rat skin permeation of various nonsteroidal antiinflammatory drugs (NSAIDs) was investigated in vitro using Franz diffusion cell at $37^{\circ}C$. The effect of various skin permeation enhancers was also observed as a preliminary study of developing transdermal delivery systems of NSAIDs. Lipophilicity of NSAIDs was determined from thε partition coefficient (log P) in 1-octanol/water and 1-octanol/IPB mutual-saturated solutions. The solubility was determined in water, isotonic phosphate buffer (IPB), and propylene glycol (PG) at $37^{\circ}C$. The rat skin permeation rate of acetaminophen, piroxicam, and aceclofenac was almost negligible, although they were saturated in PG. Addition of 1 % permeation enhancer increased the permeation rate of ketoprofen, ketorolac, and diclofenac. However, the skin permeation rate of ibuprofen did not increase with the addition of various enhancers. Among the permeation enhancers testεd, oleic acid was the most effective for various NSAIDs. Based on the daily dose, lipophilicity, and the skin permeation ratε achieved in this study, ketoprofen and ketorolac seem to be the most promising drug candidates for transdermal delivery systems, especially when formulated with unsaturated fatty acids, such as oleic acid.

• Korean Journal of Plant Tissue Culture
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• v.26 no.2
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• pp.109-113
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• 1999

To elucidate the relationship between in vitro flowering and the structure of cytokinins in ginseng (Panax ginseng C.A. Meyer), zygotic embryos, seedlings, and cotyledonary nodes were cultured on MS medium supplemented with 5 $\mu$M of various cytokinins (BA, kinetin, 2-iP, and zeatin) with or without GA$_3$ (5 $\mu$M). The frequency of in vitro flowering was the highest when explants were cultured on the medium containing BA regardless of the kinds of explants, followed by kinetin, 2-iP, and zeatin. Flowering frequency of cotyledonary node explants was significantly increased by the combined treatment of cytokinin and GA$_3$. Flowering frequency was highly correlated with the logP of cytokinins, indicating that the lipophilicity of each cytokinin may involved in the in vitro flowering of ginseng.