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2000
Volume 26, Issue 6
  • ISSN: 1389-2002
  • E-ISSN: 1875-5453

Abstract

Introduction

Shenlian formula (SL) has been widely used to treat various diseases, including type 2 diabetes mellitus and atherosclerosis (AS). Pathological states can significantly alter drug pharmacokinetics (PK) compared to normal physiology, primarily by modulating biological membrane permeability and metabolic enzyme activity, thereby affecting drug absorption, distribution, metabolism, and excretion. However, the specific influence of AS on the PK profile of SL remains uncharacterized.

Objective

To investigate the plasma PK of five components (Salvianolic acid A (SAA), Danshensu (DSS), Andrographolide (AND), Neoandrographolide (NAND), and Dehydrated andrographolide (DDAND),) which were the ingredients of SL, in physiological and AS rats administered SL intragastrically.

Methods

The AS SD rat model was induced with a high-fat diet, carotid balloon injury, and VD injections. A validated LC-MS/MS method quantified plasma concentrations to assess PK parameters.

Results and Discussion

The validation parameters were all in accordance with the current standards. Comparative PK analysis revealed significant intergroup disparities between the AS and normal groups. The value of C and AUC for DSS was significantly decreased (<0.05) in the AS group, which indicated that the absorptive amount was remarkably attenuated in the pathological state. Additionally, the variation trend of AND under C and AUC values were consistent with the alteration trend of DSS. Furthermore, the T of NAND in the AS group was significantly reduced (<0.05), confirming that the pathological state accelerated the absorption rate of NAND, thereby shortening the time required for NAND to reach its maximum concentration in the body.

Conclusion

We established and validated a sensitive LC-MS/MS method for the simultaneous quantification of five bioactive components of SL in rat plasma. This method is applicable to both physiological and pathological states. Comparative pharmacokinetic analysis revealed significant differences in the systemic exposure of all five analytes between AS and normal rats. These findings provide critical PK evidence for optimizing SL dosage regimens in AS patients, underscoring the imperative to consider the disease’ status when determining therapeutic strategies for traditional Chinese medicine formulations.

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Comparative Pharmacokinetics of Five Major Ingredients in Normal and Atherosclerotic Rats after Oral Administration of Shenlian Formula
Current Drug Metabolism 26, 402 (2025); https://doi.org/10.2174/0113892002387343250807080059
/content/journals/cdm/10.2174/0113892002387343250807080059
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  • Article Type:     Research Article
Keyword(s): Atherosclerosis; carotid balloon injury; LC-MS/MS; neoandrographolide; pharmacokinetics; Shenlian formula

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