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. 2021 Dec;59(1):1256-1259.
doi: 10.1080/13880209.2021.1942924.

Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism

Jie Zhang  1 , Lu Liu  2 , Hong Li  3 , Bin Zhang  1
Affiliations

Pharmacokinetic study on the interaction between pachymic acid and bavachin and its potential mechanism

Jie Zhang et al. Pharm Biol. 2021 Dec.

Abstract

Context: Pachymic acid and bavachin are commonly used drugs in the therapy of lung cancer.

Objective: The co-administration of pachymic acid and bavachin was investigated to evaluate their potential drug-drug interaction.

Materials and methods: The pharmacokinetics of bavachin (10 mg/kg) was studied in male Sprague-Dawley (SD) rats in the presence of pachymic acid (5 mg/kg) (n = 6). The rats without pre-treatment of pachymic acid were set as the control and the pre-treatment of pachymic acid was conducted for 7 days before the administration of bavachin. The effect of pachymic acid on the activity of CYP2C9 was also estimated in rat liver microsomes with corresponding probe substrates.

Results: Pachymic acid influenced the pharmacokinetic profile of bavachin with the increased AUC (32.82 ± 4.61 vs. 19.43 ± 3.26 μg/L/h), the prolonged t1/2 (3.21 ± 0.65 vs. 2.32 ± 0.28 h), and the decreased CLz/F (307.25 ± 44.35 vs. 523.81 ± 88.67 L/h/kg) in vivo. The metabolic stability of bavachin was enhanced by pachymic acid and the transport of bavachin was inhibited by pachymic acid. Pachymic acid was found to inhibit the activity of CYP2C9 with the IC50 of 21.25 µM as well as the activity of P-gp.

Discussion and conclusion: The interaction between pachymic acid and bavachin results from the inhibition of CYP2C9 and P-gp. The dose of bavachin should be adjusted when combining with pachymic acid. The study design can be generalized to a broader study population with adjustment in the dose.

Keywords: CYP2C9; P-gp; drug-drug interaction.

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Conflict of interest statement

The authors have no conflict of interest.

Figures

Figure 1.
Figure 1.
The mean plasma concentration-time curve of bavachin with or without the pre-treatment of pachymic acid. Pachymic acid significantly influenced the pharmacokinetic profile of bavachin.
Figure 2.
Figure 2.
Effect of pachymic acid on the transport of bavachin in Caco-2 model. Pachymic acid significantly inhibited the efflux of bavachin due to the decrease in the value of PappBA. ***p < 0.001.
Figure 3.
Figure 3.
Effect of pachymic acid on the activity of CYP2C9. Pachymic acid inhibited the activity of CYP2C9 in a dose-dependent manner with the IC50 value of 21.25 µM.
See this image and copyright information in PMC

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