Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Dec 4;12(12):1182.
doi: 10.3390/pharmaceutics12121182.

Clinical Evaluation of Acetaminophen-Galgeuntang Interaction Based on Population Approaches

Quyen Thi Tran  1 , So Jung Park  2 , Hyun-Moon Back  3 , Lien Thi Ngo  1 , Duc Tuan Cao  4 , Hung Van Nguyen  5 , Sangkeun Jung  6 , Jung-Woo Chae  1 , Yang Chun Park  2 , Hwi-Yeol Yun  1
Affiliations

Clinical Evaluation of Acetaminophen-Galgeuntang Interaction Based on Population Approaches

Quyen Thi Tran et al. Pharmaceutics. .

Abstract

Galgeuntang (GGT), a traditional herbal medicine, is widely co-administered with acetaminophen (AAP) for treatment of the common cold, but this combination has not been the subject of investigation. Therefore, we investigated the herb-drug interaction between GGT and AAP by population pharmacokinetics (PKs) modeling and simulation studies. To quantify PK parameters and identify drug interactions, an open label, three-treatment, three-period, one-sequence (AAP alone, GGT alone, and AAP and GGT in combination) clinical trial involving 12 male healthy volunteers was conducted. Ephedrine (EPD), the only GGT component detected, was identified using a one-compartment model. The PKs of AAP were described well by a one-compartment model and exhibited two-phase absorption (rapid followed by slow) and first-order elimination. The model showed that EPD significantly influenced the PKs of AAP. The simulation results showed that at an AAP dose of 1000 mg × 4 times daily, the area under the concentration versus time curve of AAP increased by 16.4% in the presence of GGT compared to AAP only. In conclusion, the PKs of AAP were affected by co-administration of GGT. Therefore, when AAP is combined with GGT, adverse effects related to overdose of AAP could be induced possibly.

Keywords: Galgeuntang; acetaminophen; drug interaction; population pharmacokinetics.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Scheme of the clinical trial. PK, pharmacokinetics.
Figure 2
Figure 2
Comparison of plasma concentration–time profiles of acetaminophen (AAP) after administration alone or co-administration with Galgeuntang (GGT). Each point represents the mean and standard deviation.
Figure 3
Figure 3
Scheme of the base model with two periods of absorption phase. CL, clearance.
Figure 4
Figure 4
Goodness of fit plots of the final AAP model. Empty circle: observation, solid line: reference line (y = x line for individual predicted concentrations (IPRED) or predicted concentrations (PRED) vs. observation plots, y = 0 for Time or IPRED vs. conditional weight residual (CWRES) plots), dash line: regression line.
Figure 5
Figure 5
Visual predictive check (VPC) plot of the final model for AAP observations. Empty circles: observed AAP concentration; pink area: 95% confidence intervals of median predicted concentration; gray areas: 95% confidence intervals of 5th and 95th percentile predicted concentration.
Figure 6
Figure 6
Simulation result of 1000 mg AAP administered alone (A) or co-administered with GGT (B) in a week. Black solid lines: median simulated concentration; shaded bands: 90% percent confidence interval for 1000 replicates simulation.
Figure 7
Figure 7
Simulation result of 1000 mg × 4 times per day of AAP administered alone (A) or co-administered with GGT (B) in a week. Black solid lines: median simulated concentration; shaded bands: 90% percent confidence interval for 1000 replicates simulation.
See this image and copyright information in PMC

References

    1. Williamson E.M. Interactions between herbal and conventional medicines. Expert Opin. Drug Saf. 2005;4:355–378. doi: 10.1517/14740338.4.2.355. - DOI - PubMed
    1. Yang T., Kim Y., Chae B. An experimental study on the anti-allergic effects, anti-inflammatory action, anti-pyretic action and analgesic action of Galgeun-tang, Gamigalgeun-tang and Geomahwanggalgeun-ang. J. Korean Orient. Med. Ophthalmol. Tolaryngol. Dermatol. 2002;15:1824.
    1. Shin J.-M., Kim Y.-O., Baek S.-H. Free radical scavenging activity and kinetic behavior of the Galgeuntang water extract. Orient. Pharm. Exp. Med. 2008;8:32–38. doi: 10.3742/OPEM.2008.8.1.032. - DOI
    1. Wu M.S., Yen H.R., Chang C.W., Peng T.Y., Hsieh C.F., Chen C.J., Lin T.Y., Horng J.T. Mechanism of action of the suppression of influenza virus replication by Ko-Ken Tang through inhibition of the phosphatidylinositol 3-kinase/Akt signaling pathway and viral RNP nuclear export. J. Ethnopharmacol. 2011;134:614–623. doi: 10.1016/j.jep.2011.01.005. - DOI - PubMed
    1. Ha H., Lee J.K., Lee M.-Y., Lim H.-S., Shin H. Galgeun-tang, an Herbal Formula, Ameliorates Atopic Dermatitis Responses in Dust Mite Extract-treated NC/Nga Mice. J. Korean Med. 2013;34:1–11. doi: 10.13048/jkm.13022. - DOI

LinkOut - more resources