Abstract:

Drug-drug interaction potentials of two herbal medicines, namely Schisandra chi nensis and Glycyrrhiza uralensis, were investigated in rats via in-vitro and in-vivo pharmacokinetic studies.Male SD rats received Schisandra or Glycyrrhiza decoction once daily for 6 days at doses equivalent to 1g or 3 g/kg. Rats receiving distil wat er and Phenobarbital (0.12 g/kg) were used as non-treatment and positive contro ls, respectively. The liver was collected for the preparation of microsomes, and P₄₅₀ levels were measured for different treatment groups. In a separate s tudy, lidocaine was employed as probe compound, and its metabolic rate in the liver mi crosomes prepared from the rats pretreated by Schisandra or Glycyrrhiza or Pheno barbital for 6 days was examined. In the in-vivo pharmacokinetic study, rats we re pretreated with Schisandra or Glycyrrhiza for 6 days. Lidocaine was administ ered on day 7 intravenously at 10 mg/kg dose. Pharmacokinetic parameters of lido caine in plasma and urine were estimated.P₄₅₀ levels in the rats pretreated by Schisandra or Glycyrrhiza were signi ficant higher than that in the non-treatment control. The increase in P₄₅₀ was dose-dependent and time-dependent. On day 6, Schisandra, Glycyrrhiza and Phen obarbital increased P₄₅₀ levels by 58%, 91% and 270% compared to the non-treatm ent control (0.695 μmol/g protein). Metabolic rate of lidocaine in the live r mi crosomes was significantly higher in rats that received Schisandra, Glycyrrhiza or Phenobarbital pretreatment when compared to the non-treatment control. Pharm acokinetic profile of lidocaine was significantly modified in the rats with the herbal pretreatment. Elimination half-lives were shorten by 28% and 39%, and to tal clearances were increased by 76% and 59% in the Schisandra and Glycyrrhiza g roups, respectively.In conclusion, Schisandra and Glycyrrhiza showed induction effect on P₄₅₀ isozymes. Efficacy and safety profiles of a drug may be affected when the herbal products or herbal prescriptions containing these two plant medicines were conc omitantly used.