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

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 ( = 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 (244.98 ± 10.95 vs. 139.18 ± 15.14 μg/L) and AUC (3295.92 ± 263.02 vs. 139.18 ± 15.14 h·μg/L) of paeoniflorin was increased by peimine. The 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 (56.78 ± 2.62 vs. 26.33 ± 3.15 min) and the decreased intrinsic clearance (24.42 ± 3.78 vs. 52.64 ± 4.47 μL/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 studies in a broader population.