阿托伐他汀升高秋水仙碱血浆浓度及潜在机制研究

Colchicine Plasma Concentration Increased by Atorvastatin and its Potential Mechanism

目的探索他汀类药物影响秋水仙碱体内药代动力学的环节及可能机制。方法采用大鼠体内药代动力学及在体肠灌流方法,利用HPLC检测血液及肠灌流液中秋水仙碱的含量,考察大鼠分别给予阿托伐他汀或维拉帕米后,秋水仙碱在肠道吸收的情况。使用DAS软件计算房室模型及相关PK参数。结果大鼠给予阿托伐他汀或维拉帕米后,秋水仙碱的C_(max)和AUC显著增加(P<0.05),但t_(max)、k_(α)、k_(10)、k_(12)、k_(21)差异无统计学意义(P>0.05)。在体肠灌流试验显示,阿托伐他汀或维拉帕米均可增加秋水仙碱的吸收参数kα和Papp(P<0.05),但对秋水仙碱的k_(α)和P_(app)的增加,阿托伐他汀与维拉帕米间差异无统计学意义(P>0.05)。结论他汀类药物可增加秋水仙碱的肠道吸收,可能是他汀类药物通过抑制P糖蛋白(P-gp)减少了秋水仙碱外排实现的。

Objective To explore the links and possible mechanisms through which statins affect colchicine pharmacokinetics in vivo.Methods In vivo pharmacokinetics and in vivo intestinal perfusion methods were used to detect the colchicine content in blood and enteroirrigation solution by HPLC.The absorption of colchicine in intestinal tract after Atorvastatin or Verapamil were respectively administered in rats was investigated.Relevant PK parameters were calculated using DAS software for the atrial model.Results Colchicine C_(max)and AUC increased significantly(P<0.05)but t_(max),k_(α),k_(10),k_(12),k_(21),were not significantly different(P>0.05)after administration of Atorvastatin or Verapamil in rats.In vivo intestinal perfusion experiments showed that Atorvastatin or Verapamil increased the absorption parameters kαand P app of colchicine(P<0.05).However,no statistically significant difference was observed bewteen Atorvastatin and Verapamil in terms of the increase in colchicines s k_(a)and P_(app)(P>0.05).Conclusion Statins increase the intestinal absorption of colchicine,which may be achieved by its reduction of colchicine efflux through inhibition of P-gp.