Effects of oral kaempferol on the pharmacokinetics of tamoxifen and one of its metabolites, 4-hydroxytamoxifen, after oral administration of tamoxifen to rats.
It has been reported that tamoxifen is a substrate of P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A, and kaempferol is an inhibitor of P-gp and CYP3A. Hence, it could be expected that kaempferol would affect the pharmacokinetics of tamoxifen. Thus, tamoxifen was administered orally (10 mg/kg) without or with oral kaempferol (2.5 and 10 mg/kg). In the presence of kaempferol, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) of tamoxifen was significantly greater, C(max) was significantly higher and F was considerably greater than those without kaempferol. The enhanced bioavailability of oral tamoxifen by oral kaempferol could have been due to an inhibition of CYP3A and P-gp by kaempferol. The presence of kaempferol did not alter the pharmacokinetic parameters of a metabolite of tamoxifen, 4-hydroxytamoxifen. This could have been because the contribution of CYP3A to the formation of 4-hydroxytamoxifen is not considerable in rats.
Piao
Yongji
Y
College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
Shin
Sang-Chul
SC
Choi
Jun-Shik
JS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000284:Administration, Oral; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D044949:Kaempferols / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018931:Antineoplastic Agents, Hormonal; D065692:Cytochrome P-450 CYP3A Inhibitors; D044949:Kaempferols; D013629:Tamoxifen; C016601:afimoxifene; C006552:kaempferol