In Vitro assessment of clarithromycin and erythromycin depletion in the presence of andrographolide using human liver microsomes
Abstract
ObjectiveAndrographolide is a major bioactive compound of Andrographis paniculata, a medicinal herb widely used in Asia. Previous in vitro studies have reported effects of andrographolide on CYP3A4 expression and activity. However, potential pharmacokinetic interactions with the macrolide antibiotics clarithromycin and erythromycin remain poorly characterized. This study investigated the effect of andrographolide on their in vitro depletion using pooled human liver microsomes (HLMs).MethodsClarithromycin and erythromycin (1 µM each) were incubated in pooled HLMs with or without andrographolide at 2, 10, or 20 μM, corresponding to approximately 10-, 50-, and 100-fold the reported peak concentration (Cmax), respectively. Parent-antibiotic depletion was monitored by LC-MS/MS, and depletion rates were estimated by linear regression.ResultsAndrographolide did not significantly alter clarithromycin depletion at two or 10 µM (p = 0.1906 and 0.7898), whereas a significant difference was observed at 20 µM (p = 0.0321). The estimated effects had wide 95% confidence intervals. Erythromycin depletion was significantly altered at all concentrations, with relative differences of 38.5% (95% CI, 28.5%–48.5%), 33.5% (28.6%–38.3%), and 66.2% (57.0%–75.5%) at 2, 10, and 20 μM, respectively (all p < 0.0001).ConclusionAndrographolide exerts a strong, concentration-dependent effect on in vitro erythromycin depletion in HLMs, whereas its effect on clarithromycin depletion is minimal and observed only at supra-therapeutic concentrations (100-fold Cmax). Given that effective concentrations exceeded physiological Cmax levels, clinical relevance remains uncertain. Further investigation is needed to clarify underlying metabolic mechanisms and evaluate in vivo translation.
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BibTeX
@article{tipthara2026vitro,
title = {{In Vitro assessment of clarithromycin and erythromycin depletion in the presence of andrographolide using human liver microsomes}},
author = {Phornpimon Tipthara and Siribha Apinan and Rattawan Kullasakboonsri and Kanyarat Sueksakit and Onrapak Reamtong and Joel Tarning},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1983947},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1983947},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - In Vitro assessment of clarithromycin and erythromycin depletion in the presence of andrographolide using human liver microsomes
AU - Phornpimon Tipthara
AU - Siribha Apinan
AU - Rattawan Kullasakboonsri
AU - Kanyarat Sueksakit
AU - Onrapak Reamtong
AU - Joel Tarning
PY - 2026
DA - 2026/11/02
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1983947
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1983947
AB - ObjectiveAndrographolide is a major bioactive compound of Andrographis paniculata, a medicinal herb widely used in Asia. Previous in vitro studies have reported effects of andrographolide on CYP3A4 expression and activity. However, potential pharmacokinetic interactions with the macrolide antibiotics clarithromycin and erythromycin remain poorly characterized. This study investigated the effect of andrographolide on their in vitro depletion using pooled human liver microsomes (HLMs).MethodsClarithromycin and erythromycin (1 µM each) were incubated in pooled HLMs with or without andrographolide at 2, 10, or 20 μM, corresponding to approximately 10-, 50-, and 100-fold the reported peak concentration (Cmax), respectively. Parent-antibiotic depletion was monitored by LC-MS/MS, and depletion rates were estimated by linear regression.ResultsAndrographolide did not significantly alter clarithromycin depletion at two or 10 µM (p = 0.1906 and 0.7898), whereas a significant difference was observed at 20 µM (p = 0.0321). The estimated effects had wide 95% confidence intervals. Erythromycin depletion was significantly altered at all concentrations, with relative differences of 38.5% (95% CI, 28.5%–48.5%), 33.5% (28.6%–38.3%), and 66.2% (57.0%–75.5%) at 2, 10, and 20 μM, respectively (all p < 0.0001).ConclusionAndrographolide exerts a strong, concentration-dependent effect on in vitro erythromycin depletion in HLMs, whereas its effect on clarithromycin depletion is minimal and observed only at supra-therapeutic concentrations (100-fold Cmax). Given that effective concentrations exceeded physiological Cmax levels, clinical relevance remains uncertain. Further investigation is needed to clarify underlying metabolic mechanisms and evaluate in vivo translation.
SN - 1663-9812
ER -