Bufalin inhibits CYP3A4 activity in vitro and in vivo.
OBJECTIVE
To investigate the inhibitory interactions of bufalin and CYP3A4.


METHODS
Recombinant human CYP3A4 was incubated with bufalin in vitro. Bufalin was administered ig and iv to Wistar rats to further estimate its impact on CYP3A4, and midazolam was given to index the activity of CYP3A4.


RESULTS
The IC(50) of bufalin was 14.52 micromol/L. Bufalin affected CYP3A4 activity with increases in AUC(0-t) and t(1/2), and decreases in CL and the formation of 1-hydroxy-midazolam after ig or iv administration of midazolam (P<0.05). An increase in C(max) after ig bufalin administration (P<0.05) was observed.


CONCLUSIONS
Bufalin showed a modest but significant inhibition of CYP3A4 both in vitro and in vivo. The likelihood of an interaction between bufalin and the CYP3A4-metabolized drugs in human might not be negated.
Li
Hai-yun
HY
Department of Natural Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Xu
Wen
W
Zhang
Xi
X
Zhang
Wei-dong
WD
Hu
Li-wei
LW
D000818:Animals; D002018:Bufanolides / Q000008:administration & dosage / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000008:administration & dosage; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors
D002018:Bufanolides; D065692:Cytochrome P-450 CYP3A Inhibitors; D004365:Drugs, Chinese Herbal; D011994:Recombinant Proteins; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D008874:Midazolam; C022777:bufalin