Abstract
Naoxintong capsule (NXT), a prescribed Chinese medicine, has been used clinically for more than 20 years and is widely received by patients. We determined five probe drugs, namely, omeprazole (CYP2C19), midazolam (CYP3A4), phenacetin (CYP1A2), tolbutamide (CYP2C9), and dextromethorphan (CYP2D6) to study the potential influences of NXT on the activities of CYP enzymes and assessed the pharmacokinetics effect of NXT on metoprolol tartrate in rat plasma. The study showed that AUC(0–24) and AUC(0–∞) of midazolam (CYP3A4) in NXT coadministration group (283.7 ± 65.2 h·ng·mL−1 and 292.0 ± 75.1 h·ng·mL−1 in group B; 295.7 ± 62.7 h·ng·mL−1 and 299.5 ± 60.0 h·ng·mL−1 in group C) were significantly decreased as compared to another group (416.8 ± 82.3 h·ng·mL−1 and 424.9 ± 77.9 h·ng·mL−1 in group A), while that of dextromethorphan (CYP2D6) showed an opposite tendency (540.7 ± 119.7 h·ng·mL−1 and 595.3 ± 122.2 h·ng·mL−1 in group A, 760.6 ± 184.9 h·ng·mL−1 and 788.7 ± 211.0 h·ng·mL−1 in group B, and 734.3 ± 118.5 h·ng·mL−1 and 757.2 ± 105.4 h·ng·mL−1 in group C). Moreover, NXT preadministration can enhance the metabolism of metoprolol tartrate and reduce the metabolism of O-demethylmetoprolol. The results indicated that NXT had potential effects in inducing CYP3A4 and inhibiting CYP2D6 in the metabolism of metoprolol tartrate. It suggests that patients who coadministered NXT and metoprolol tartrate should be advised of potential herb-drug interactions (HDIs) to reduce therapeutic failure or accelerated toxicity of conventional drug treatment.
Highlights
Chinese medicinal herbs (CMHs) have been used for cerebrovascular disease clinically because of its fewer side effects and multitargeted effects [1]
Effect of Naoxintong capsule (NXT) on Five Probe Drugs in Rats. is experiment studied the effect of NXT on omeprazole (CYP2C19), midazolam (CYP3A4), phenacetin (CYP1A2), tolbutamide (CYP2C9), and dextromethorphan (CYP2D6) in different treatment groups as mentioned in Section 2.2. e pharmacokinetic parameters and mean plasma concentrationtime curves of the five probe drugs are shown in Table 3 and Figure 2
As compared to group A (122412.8 ± 25958.5 h·ng·mL− 1), the AUC(0–24) of tolbutamide in group B (124685.2 ±19824.0 h·ng·mL− 1) and C (112713.7 ± 19708.0 h·ng·mL− 1) showed that there was no significant influence in the different treatment groups. ese results implied that NXT showed little alteration on CYP2C9 activity in vivo
Summary
Chinese medicinal herbs (CMHs) have been used for cerebrovascular disease clinically because of its fewer side effects and multitargeted effects [1]. NXT is a famous Chinese medicine for the treatment of cardiovascular diseases in clinic for more than 20 years [2, 3] and is composed of 16 CMHs including Radix Angelicae Sinensis (Danggui), Commiphora myrrha Eng (Moyao), Radix Paeoniae (Chishao), Semen Persicae (Taoren), Salviae miltiorrhizae Radix et Rhizoma (Danshen), and Achyranthes bidentata (Niuxi) [4]. NXT has been widely used in treating atherosclerosis, cerebrovascular diseases, blood stasis syndrome, qi deficiency, and coronary heart diseases [7]. It has increased popularity as a coadministered treatment with other prescription drugs.
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