{"title":"使用增溶剂和生物增强剂提高穿心莲内酯的口服生物利用度:穿心莲制剂在小猎犬体内的药代动力学比较。","authors":"Phanit Songvut, Tussapon Boonyarattanasoonthorn, Nitra Nuengchamnong, Thammaporn Junsai, Teetat Kongratanapasert, Kittitach Supannapan, Phisit Khemawoot","doi":"10.1080/13880209.2024.2311201","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility.</p><p><strong>Objective: </strong>This work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in <i>Andrographis paniculata</i> (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer.</p><p><strong>Materials and methods: </strong>Four groups of beagles were compared: (1) <i>A. paniculata</i> powder alone (control), (2) <i>A. paniculata</i> powder with 50% weight/weight (w/w) β-cyclodextrin solubilizer, (3) <i>A. paniculata</i> powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) <i>A. paniculata</i> powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. All groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days.</p><p><strong>Results: </strong>Thirteen chemical compounds were identified in <i>A. paniculata</i> powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. <i>A. paniculata</i> co-administration with either 50% w/w β-cyclodextrin or 1% w/w SDS, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces.</p><p><strong>Conclusion: </strong>The combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for <i>A. paniculata</i> formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"183-194"},"PeriodicalIF":3.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868414/pdf/","citationCount":"0","resultStr":"{\"title\":\"Enhancing oral bioavailability of andrographolide using solubilizing agents and bioenhancer: comparative pharmacokinetics of <i>Andrographis paniculata</i> formulations in beagle dogs.\",\"authors\":\"Phanit Songvut, Tussapon Boonyarattanasoonthorn, Nitra Nuengchamnong, Thammaporn Junsai, Teetat Kongratanapasert, Kittitach Supannapan, Phisit Khemawoot\",\"doi\":\"10.1080/13880209.2024.2311201\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility.</p><p><strong>Objective: </strong>This work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in <i>Andrographis paniculata</i> (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer.</p><p><strong>Materials and methods: </strong>Four groups of beagles were compared: (1) <i>A. paniculata</i> powder alone (control), (2) <i>A. paniculata</i> powder with 50% weight/weight (w/w) β-cyclodextrin solubilizer, (3) <i>A. paniculata</i> powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) <i>A. paniculata</i> powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. All groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days.</p><p><strong>Results: </strong>Thirteen chemical compounds were identified in <i>A. paniculata</i> powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. <i>A. paniculata</i> co-administration with either 50% w/w β-cyclodextrin or 1% w/w SDS, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces.</p><p><strong>Conclusion: </strong>The combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for <i>A. paniculata</i> formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted.</p>\",\"PeriodicalId\":19942,\"journal\":{\"name\":\"Pharmaceutical Biology\",\"volume\":\"62 1\",\"pages\":\"183-194\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868414/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13880209.2024.2311201\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13880209.2024.2311201","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Enhancing oral bioavailability of andrographolide using solubilizing agents and bioenhancer: comparative pharmacokinetics of Andrographis paniculata formulations in beagle dogs.
Context: The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility.
Objective: This work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in Andrographis paniculata (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer.
Materials and methods: Four groups of beagles were compared: (1) A. paniculata powder alone (control), (2) A. paniculata powder with 50% weight/weight (w/w) β-cyclodextrin solubilizer, (3) A. paniculata powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) A. paniculata powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. All groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days.
Results: Thirteen chemical compounds were identified in A. paniculata powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. A. paniculata co-administration with either 50% w/w β-cyclodextrin or 1% w/w SDS, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces.
Conclusion: The combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for A. paniculata formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted.
期刊介绍:
Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine.
Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.