| RRC ID |
1994
|
| Author |
Yoshida N, Takagi A, Kitazawa H, Kawakami J, Adachi I.
|
| Title |
Effects of citronellal, a monoterpenoid in Zanthoxyli Fructus, on the intestinal absorption of digoxin in vitro and in vivo.
|
| Journal |
J Pharm Sci
|
| Abstract |
Complementary and alternative medicines can be applied concomitantly with conventional medicines; however, little drug information is available on these interactions. Previously, we reported on the inhibitory effects of an extract and monoterpenoids (e.g., (R)-(+)-citronellal) contained in citrus herbs on P-glycoprotein (P-gp) using P-gp-overexpressed LLC-PK1 cells. The objective of the present study was to investigate the effects of (R)-(+)-citronellal on P-gp-mediated transport in the intestinal absorption process in vitro and in vivo. Transcellular transport of [(3)H]digoxin across Caco-2 cell monolayers was measured in the presence or absence of (R)-(+)-citronellal. (R)-(+)-citronellal reduced the basolateral-to-apical transport and efflux ratio for [(3)H]digoxin significantly. Serum concentration-time profiles and pharmacokinetic parameters of digoxin after intravenous and oral administration were analyzed in rats pretreated with oral (R)-(+)-citronellal. The bioavailability of digoxin after oral administration decreased significantly to 75.8% of that after intravenous administration at the same dose. (R)-(+)-citronellal increased the bioavailability of oral digoxin to 99.9% but had no effects on total body clearance, volume of distribution, or elimination rate. These findings suggest that (R)-(+)-citronellal can increase the bioavailability of oral digoxin based on the blockade of P-gp-mediated efflux of digoxin from intestinal epithelia to the lumen in the absorption process.
|
| Volume |
95(3)
|
| Pages |
552-60
|
| Published |
2006-3-1
|
| DOI |
10.1002/jps.20563
|
| PII |
S0022-3549(16)31975-X
|
| PMID |
16419049
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Acyclic Monoterpenes
Aldehydes / pharmacology*
Animals
Biological Availability
Caco-2 Cells
Digoxin / blood
Digoxin / pharmacokinetics*
Humans
Intestinal Absorption / drug effects*
Male
Monoterpenes / pharmacology*
Rats
Rats, Wistar
Zanthoxylum / chemistry
|
| IF |
2.997
|
| Times Cited |
2
|
|
WOS Category
|
CHEMISTRY, MULTIDISCIPLINARY
PHARMACOLOGY & PHARMACY
CHEMISTRY, MEDICINAL
|
| Resource |
| Human and Animal Cells |
CACO-2(RCB0988) |
