Pharmacokinetic interaction between peimine and paeoniflorin in rats and its potential mechanism

Abstract

Context: Peimine and paeoniflorin can be combined for the treatment of cough in paediatrics. The interaction during the co-administration could dramatically affect the bioavailability of drugs. Objective: The interaction between peimine and paeoniflorin was investigated in this study. Materials and methods: The pharmacokinetics of paeoniflorin (20 mg/kg) with or without the coadministration of peimine (5 mg/kg for 10 days before paeoniflorin) was orally investigated in Sprague-Dawley rats (n ¼ 6). The group without the peimine was set as the control group. The metabolic stability of paeoniflorin was studied in rat liver with microsomes. The effect of peimine on the absorption of paeoniflorin was investigated with Caco-2 cell monolayers. Results: The C max (244.98 ± 10.95 vs. 139.18 ± 15.14 lg/L) and AUC (0-t) (3295.92 ± 263.02 vs. 139.18 ± 15.14 hÁlg/L) of paeoniflorin was increased by peimine. The t 1/2 was prolonged from 5.33 ± 1.65 to 14.21 ± 4.97 h and the clearance was decreased from 15.43 ± 1.75 to 4.12 ± 0.57 L/h/kg. Consistently, peimine increased the metabolic stability of paeoniflorin with rat liver microsomes with the increased t 1/2 (56.78 ± 2.62 vs. 26.33 ± 3.15 min) and the decreased intrinsic clearance (24.42 ± 3.78 vs. 52.64 ± 4.47 lL/ min/mg protein). Moreover, the transportation of paeoniflorin was also inhibited by peimine as the efflux ratio decreased from 3.06 to 1.63. Discussion and conclusions: Peimine increased the systemic exposure of paeoniflorin through inhibiting the activity of CYP3A4 and P-gp. These results provide a reference for further in vivo studies in a broader population.

Baicalein inhibits the pharmacokinetics of simvastatin in rats via regulating the activity of CYP3A4

“…Co-administration of different drugs might lead to therapy failure and even toxicity resulting from interactions between co-administrated drugs. For example, the combination of peimine and paeoniflorin for the treatment of cough could cause the increased plasma concentration of paeoniflorin in rats implying the drug-drug interaction between peimine and paeoniflorin (Chen et al 2021). The co-intravenous administration of Shuanghuanglian and azithromycin could increase the drug exposure of each other and might improve the therapy efficiency of these two injections (Tian et al 2019).…”

Protective effects of paeoniflorin on cardiovascular diseases: A pharmacological and mechanistic overview

“…Most paeoniflorin is mainly eliminated in the urine via glomerular filtration of the renal system ( Cheng et al, 2016 ). As experimental data collected from rats show, the serum concentration of paeoniflorin is dose-dependent, with a half-life (T1/2) of approximately 1.8 h ( Fei et al, 2016 ; Chen et al, 2021 ). In traditional Chinese medicine, Chinese herbal preparations made by combinations of various kinds of botanical drugs can usually achieve the role of synergistic effect and attenuation of toxicity.…”

The pharmacokinetic study on the interaction between nobiletin and anemarsaponin BII in vivo and in vitro

“…For example, peimine and paeoniflorin are the major extractions of herbs used for cough in paediatrics, and the co-administration of these two compounds results in the inhibition of the metabolism of paeoniflorin (Chen et al. 2021 ). The interaction between nobiletin and anemarsaponin BII was clear, which is of great importance for the clinical combination of C. reticulata .…”