Evaluation of the impact of cantharidin on rat CYP enzymes by using a cocktail of probe drugs.
The aim of this study was to assess the influence of cantharidin on the activities of the drug-metabolizing enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 in rats. The activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 were measured using specific probe drugs. After pretreatment for 1week with cantharidin or physiological saline (control group) by intraperitoneal injection, probe drugs phenacetin (5.0mg/kg; CYP1A2 activity), tolbutamide (1.0mg/kg; CYP2C9 activity), omeprazole (10mg/kg; CYP2C19 activity), metoprolol (20mg/kg; CYP2D6 activity) and midazolam (10mg/kg; CYP3A4 activity) were administered to rats by oral administration. The blood was then collected at different times for ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. The data showed that cantharidin exhibits an inhibitory effect on CYP2D6 and CYP3A4 by increasing t1/2, Cmax and AUC(0-∞), and decreasing CL/F compared with those of the control group. In addition, cantharidin has induction effect on CYP2C9 activity. However, no significant changes in CYP1A2 and CYP2C19 activities were observed. In conclusion, the results indicated that cantharidin could inhibit CYP2D6 and CYP3A4, while induce CYP2C9, which may affect the disposition of medicines primarily dependent on these pathways. Our work may be the basis of related herb-drug interactions in the clinic.
Wenzhou Central Hospital, Wenzhou 325000, PR China.
Chen-Jian
CJ
Zhou
The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, PR China.
Li-Man
LM
Qiao
The People's Hospital of Wenzhou, Wenzhou 325000, PR China.
Lang-Huan
LH
Zhao
Wenzhou Central Hospital, Wenzhou 325000, PR China. Electronic address: wzlizhenyue@163.com.
Zhen-Yue
ZY
Li
D000818:Animals; D002193:Cantharidin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D065698:Cytochrome P-450 CYP2C9 Inducers; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D065693:Cytochrome P-450 Enzyme Inducers / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D041743:Herb-Drug Interactions; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
D065698:Cytochrome P-450 CYP2C9 Inducers; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D065693:Cytochrome P-450 Enzyme Inducers; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D002193:Cantharidin
CYP; Cantharidin; Cocktail; Plasma; UPLC–MS/MS