Enhancing oral bioavailability of andrographolide using solubilizing agents and bioenhancer: comparative pharmacokinetics of Andrographis paniculata formulations in beagle dogs

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:比格犬中穿心莲制剂的药代动力学比较

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作者:Phanit Songvut, Tussapon Boonyarattanasoonthorn, Nitra Nuengchamnong, Thammaporn Junsai, Teetat Kongratanapasert, Kittitach Supannapan, Phisit Khemawoot

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.

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.

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

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.

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