Partitioning of Anti-inflammatory Steroid Drugs into Phosphatidylcholine and Phosphatidylcholine-Cholesterol Small Unilamellar Vesicles as Studied by Second-Derivative Spectrophotometry
The partition coefficients (Kps) of six anti-inflammatory steroid drugs, dexamethasone (DMS), betamethasone (BMS), triamcinolone acetonide (TCLA), fluocinolone acetonide (FCLA), betamethasone 17,21-dipropionate (BMSDP), and clobetasole propionate (CBSP), for phosphatidylcholine (PC), and PC-choleste...
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| Veröffentlicht in: | Chemical & pharmaceutical bulletin 2008/05/01, Vol.56(5), pp.663-667 |
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| creator | Takegami, Shigehiko Kitamura, Keisuke Funakoshi, Takako Kitade, Tatsuya |
| description | The partition coefficients (Kps) of six anti-inflammatory steroid drugs, dexamethasone (DMS), betamethasone (BMS), triamcinolone acetonide (TCLA), fluocinolone acetonide (FCLA), betamethasone 17,21-dipropionate (BMSDP), and clobetasole propionate (CBSP), for phosphatidylcholine (PC), and PC-cholesterol small unilamellar vesicles (SUVs) were determined by a second-derivative spectrophotometric method. The Kp values were obtained with a relative standard deviation of below 10% and the following order was observed: BMS≤DMS |
| doi_str_mv | 10.1248/cpb.56.663 |
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The Kp values were obtained with a relative standard deviation of below 10% and the following order was observed: BMS≤DMS<TCLA<FCLA<<BMSDP<CBSP. BMSDP which has a structure that the two hydroxyl groups of BMS are esterified with propionic acid showed a largely enhanced Kp value of 10.5 times that of BMS. Further, replacement of a propionate group in BMSDP with a chlorine atom resulted in the highest Kp value (CBSP) within the drugs examined, i.e., the Kp value of CBSP was 1.2 times that of BMSDP. The presence of 30 mol% cholesterol in the SUV bilayers reduced these Kp values to approximately 35—50% of those values for the PC SUVs, although the order of the Kp values remained unchanged. The order of the Kp values agreed with that of the reported dermatological therapeutic potency of these drugs, although the order of their log P values for n-octanol/water systems showed a discrepancy. Our results indicate that the potency of steroid drugs in dermatological treatments depends to some extent on the Kp values of the drug, that is, the affinity of steroid drugs for PC bilayers influences their clinical potency, since potency is related to transdermal absorption.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.56.663</identifier><identifier>PMID: 18451554</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Algorithms ; Anti-Inflammatory Agents - chemistry ; Chemical Phenomena ; Chemistry, Physical ; Cholesterol - chemistry ; Dermatologic Agents - chemistry ; dermatological therapeutic potency ; Drug Carriers ; Drug Compounding ; Indicators and Reagents ; liposome ; Membranes, Artificial ; Particle Size ; partition coefficient ; Phosphatidylcholines - chemistry ; Phosphorus - analysis ; second-derivative spectrophotometry ; Spectrophotometry, Ultraviolet ; steroid drug ; Steroids - chemistry</subject><ispartof>Chemical and Pharmaceutical Bulletin, 2008/05/01, Vol.56(5), pp.663-667</ispartof><rights>2008 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-8c6a6c644ea11572163cd477af88a558ecfcd4ed752f3c774d209fd177ecd76a3</citedby><cites>FETCH-LOGICAL-c495t-8c6a6c644ea11572163cd477af88a558ecfcd4ed752f3c774d209fd177ecd76a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18451554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takegami, Shigehiko</creatorcontrib><creatorcontrib>Kitamura, Keisuke</creatorcontrib><creatorcontrib>Funakoshi, Takako</creatorcontrib><creatorcontrib>Kitade, Tatsuya</creatorcontrib><title>Partitioning of Anti-inflammatory Steroid Drugs into Phosphatidylcholine and Phosphatidylcholine-Cholesterol Small Unilamellar Vesicles as Studied by Second-Derivative Spectrophotometry</title><title>Chemical & pharmaceutical bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><description>The partition coefficients (Kps) of six anti-inflammatory steroid drugs, dexamethasone (DMS), betamethasone (BMS), triamcinolone acetonide (TCLA), fluocinolone acetonide (FCLA), betamethasone 17,21-dipropionate (BMSDP), and clobetasole propionate (CBSP), for phosphatidylcholine (PC), and PC-cholesterol small unilamellar vesicles (SUVs) were determined by a second-derivative spectrophotometric method. The Kp values were obtained with a relative standard deviation of below 10% and the following order was observed: BMS≤DMS<TCLA<FCLA<<BMSDP<CBSP. BMSDP which has a structure that the two hydroxyl groups of BMS are esterified with propionic acid showed a largely enhanced Kp value of 10.5 times that of BMS. Further, replacement of a propionate group in BMSDP with a chlorine atom resulted in the highest Kp value (CBSP) within the drugs examined, i.e., the Kp value of CBSP was 1.2 times that of BMSDP. The presence of 30 mol% cholesterol in the SUV bilayers reduced these Kp values to approximately 35—50% of those values for the PC SUVs, although the order of the Kp values remained unchanged. The order of the Kp values agreed with that of the reported dermatological therapeutic potency of these drugs, although the order of their log P values for n-octanol/water systems showed a discrepancy. Our results indicate that the potency of steroid drugs in dermatological treatments depends to some extent on the Kp values of the drug, that is, the affinity of steroid drugs for PC bilayers influences their clinical potency, since potency is related to transdermal absorption.</description><subject>Algorithms</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Chemical Phenomena</subject><subject>Chemistry, Physical</subject><subject>Cholesterol - chemistry</subject><subject>Dermatologic Agents - chemistry</subject><subject>dermatological therapeutic potency</subject><subject>Drug Carriers</subject><subject>Drug Compounding</subject><subject>Indicators and Reagents</subject><subject>liposome</subject><subject>Membranes, Artificial</subject><subject>Particle Size</subject><subject>partition coefficient</subject><subject>Phosphatidylcholines - chemistry</subject><subject>Phosphorus - analysis</subject><subject>second-derivative spectrophotometry</subject><subject>Spectrophotometry, Ultraviolet</subject><subject>steroid drug</subject><subject>Steroids - chemistry</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkV2LEzEUhoMobl298QdIQNgLYWoyk4_plSxdv2DBhbrehjQ500mZScYks9Cf5r8zpdUF8SaHJA_POcmL0GtKlrRm7XszbZdcLIVonqAFbZiseF03T9GCELKq6kY0F-hFSntCak5k8xxd0JZxyjlboF93OmaXXfDO73Do8LXPrnK-G_Q46hziAW8yxOAsvonzLmHnc8B3fUhTr7Ozh8H0YXAesPb2f-fVulRIR8eAN6MeBnzvXbHDMOiIf0ByptxjnUqj2TqweFt6ggneVjcQ3UPRPQDeTGByDFMfchghx8NL9KzTQ4JX53qJ7j99_L7-Ut1--_x1fX1bGbbiuWqN0MIIxkBTymVNRWMsk1J3bas5b8F0ZQ9W8rprjJTM1mTVWSolGCuFbi7R1ck7xfBzLi9Ro0vmOL2HMCclVkXJalHAt_-A-zBHX2ZTlAnCKJMrUqh3J8rEkFKETk3RjToeFCXqGKcqcSouVImzwG_Oynk7gn1Ez_kV4MMJ2Kesd_AXOIZavvWPi5-Wony86XVU4JvfGmm38A</recordid><startdate>20080501</startdate><enddate>20080501</enddate><creator>Takegami, Shigehiko</creator><creator>Kitamura, Keisuke</creator><creator>Funakoshi, Takako</creator><creator>Kitade, Tatsuya</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20080501</creationdate><title>Partitioning of Anti-inflammatory Steroid Drugs into Phosphatidylcholine and Phosphatidylcholine-Cholesterol Small Unilamellar Vesicles as Studied by Second-Derivative Spectrophotometry</title><author>Takegami, Shigehiko ; Kitamura, Keisuke ; Funakoshi, Takako ; Kitade, Tatsuya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-8c6a6c644ea11572163cd477af88a558ecfcd4ed752f3c774d209fd177ecd76a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Algorithms</topic><topic>Anti-Inflammatory Agents - chemistry</topic><topic>Chemical Phenomena</topic><topic>Chemistry, Physical</topic><topic>Cholesterol - chemistry</topic><topic>Dermatologic Agents - chemistry</topic><topic>dermatological therapeutic potency</topic><topic>Drug Carriers</topic><topic>Drug Compounding</topic><topic>Indicators and Reagents</topic><topic>liposome</topic><topic>Membranes, Artificial</topic><topic>Particle Size</topic><topic>partition coefficient</topic><topic>Phosphatidylcholines - chemistry</topic><topic>Phosphorus - analysis</topic><topic>second-derivative spectrophotometry</topic><topic>Spectrophotometry, Ultraviolet</topic><topic>steroid drug</topic><topic>Steroids - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takegami, Shigehiko</creatorcontrib><creatorcontrib>Kitamura, Keisuke</creatorcontrib><creatorcontrib>Funakoshi, Takako</creatorcontrib><creatorcontrib>Kitade, Tatsuya</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takegami, Shigehiko</au><au>Kitamura, Keisuke</au><au>Funakoshi, Takako</au><au>Kitade, Tatsuya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Partitioning of Anti-inflammatory Steroid Drugs into Phosphatidylcholine and Phosphatidylcholine-Cholesterol Small Unilamellar Vesicles as Studied by Second-Derivative Spectrophotometry</atitle><jtitle>Chemical & pharmaceutical bulletin</jtitle><addtitle>Chem. Pharm. Bull.</addtitle><date>2008-05-01</date><risdate>2008</risdate><volume>56</volume><issue>5</issue><spage>663</spage><epage>667</epage><pages>663-667</pages><issn>0009-2363</issn><eissn>1347-5223</eissn><abstract>The partition coefficients (Kps) of six anti-inflammatory steroid drugs, dexamethasone (DMS), betamethasone (BMS), triamcinolone acetonide (TCLA), fluocinolone acetonide (FCLA), betamethasone 17,21-dipropionate (BMSDP), and clobetasole propionate (CBSP), for phosphatidylcholine (PC), and PC-cholesterol small unilamellar vesicles (SUVs) were determined by a second-derivative spectrophotometric method. The Kp values were obtained with a relative standard deviation of below 10% and the following order was observed: BMS≤DMS<TCLA<FCLA<<BMSDP<CBSP. BMSDP which has a structure that the two hydroxyl groups of BMS are esterified with propionic acid showed a largely enhanced Kp value of 10.5 times that of BMS. Further, replacement of a propionate group in BMSDP with a chlorine atom resulted in the highest Kp value (CBSP) within the drugs examined, i.e., the Kp value of CBSP was 1.2 times that of BMSDP. The presence of 30 mol% cholesterol in the SUV bilayers reduced these Kp values to approximately 35—50% of those values for the PC SUVs, although the order of the Kp values remained unchanged. The order of the Kp values agreed with that of the reported dermatological therapeutic potency of these drugs, although the order of their log P values for n-octanol/water systems showed a discrepancy. Our results indicate that the potency of steroid drugs in dermatological treatments depends to some extent on the Kp values of the drug, that is, the affinity of steroid drugs for PC bilayers influences their clinical potency, since potency is related to transdermal absorption.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>18451554</pmid><doi>10.1248/cpb.56.663</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Algorithms Anti-Inflammatory Agents - chemistry Chemical Phenomena Chemistry, Physical Cholesterol - chemistry Dermatologic Agents - chemistry dermatological therapeutic potency Drug Carriers Drug Compounding Indicators and Reagents liposome Membranes, Artificial Particle Size partition coefficient Phosphatidylcholines - chemistry Phosphorus - analysis second-derivative spectrophotometry Spectrophotometry, Ultraviolet steroid drug Steroids - chemistry |
| title | Partitioning of Anti-inflammatory Steroid Drugs into Phosphatidylcholine and Phosphatidylcholine-Cholesterol Small Unilamellar Vesicles as Studied by Second-Derivative Spectrophotometry |
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