The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers.
The effects of berberine (BBR) on the pharmacokinetics of ciclosporin A (CsA) were examined in healthy volunteers. Six healthy male volunteers were orally treated with 0.3 g BBR, twice daily for 10 days. Pharmacokinetic investigations on CsA at 6 mg/kg were done both before and at the end of the BBR treatment period. Another six healthy male volunteers were involved in the pharmacokinetic study with 3 mg CsA/kg, in which the subjects orally received the second single dose of 3 mg CsA/kg, followed by a single oral dose of 0.3 g BBR. The blood CsA concentrations were determined by fluorescence polarization immunoassay. In the pharmacokinetic study with 6 mg CsA/kg, BBR caused no significant changes in the pharmacokinetic parameters of CsA. However, in the trial with 3 mg CsA/kg, the average percentage increase in area under the blood concentration-time curve of CsA was 19.2% (P < 0.05) and the mean C12 increased to 123 microg/l from 104 microg/l (P < 0.05), without altering elimination half-life (t(1/2)), maximum blood drug concentration (Cmax), time to Cmax (tmax), apparent oral clearance (CL/F). The present results suggest that BBR can increase the oral bioavailability of CsA at the dosage of 3 mg/kg. The BBR-mediated increase in CsA bioavailability may be partly attributed to a decrease in liver and/or intestinal metabolism through the inhibition of CYP3A4 in the liver and/or gut wall. The BBR-induced increase in emptying time of stomach and small intestine might be another reason for the increase in CsA bioavailability. However, the speculation should be proved by further investigation.
Xin
H-W
HW
Department of Clinical Pharmacology, Wuhan General Hospital, Wuhan, People's Republic of China.
Wu
X-C
XC
Li
Q
Q
Yu
A-R
AR
Zhong
M-Y
MY
Liu
Y-Y
YY
D000328:Adult; D001599:Berberine / Q000494:pharmacology*; D001682:Biological Availability; D016572:Cyclosporine / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005746:Gastric Emptying / Q000187:drug effects; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D001599:Berberine; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human