Abstract
Purpose: Raloxifene is a selective estrogen receptor modulator which is structurally similar to tamoxifen. As flavonoids can interact with raloxifene in vitro, we evaluated the in vivo pharmacokinetics of raloxifene in rats when co-administered with apigenin. Methods: The pharmacokinetics of raloxifene in the absence or presence of apigenin was investigated in rats after different dosage regimens. The plasma concentrations before and after enzymatic hydrolysis were analyzed by HPLC, and the pharmacokinetic profiles of raloxifene administered alone and in combination with apigenin were compared. Results: Co-administration of apigenin with raloxifene in a 1:2 ratio by weight resulted in a 55% and 37% increase in the Cmax and AUC of intact raloxifene, respectively. When equal proportions of raloxifene and apigenin (1:1) were administered, the Cmax and AUC of intact raloxifene were increased by 173% and 97% respectively. This increase in intact raloxifene was not associated with an increase in total raloxifene (intact plus conjugated raloxifene) because AUC and Cmax of total raloxifene when administered alone or in combination with apigenin were found to be similar. The results indicated that apigenin inhibited the glucuronidation and sulfation of raloxifene in the intestine bringing about an increased bioavailability of the drug. Conclusions: The results showed that apigenin decreased the first-pass metabolism of raloxifene but did not increase its absorption from the gastrointestinal tract.
Highlights
Raloxifene is a selective estrogen receptor modulator (SERM) that produces both estrogenagonistic effects on bone and lipid metabolism and estrogen-antagonistic effects on the uterine endometrium and breast tissue
The plasma concentration-time profiles of raloxifene in different dosage regimens before and after enzymatic hydrolysis are shown in Figures 1 and 2
The analysis of variance of t1/2 and tmax showed no differences (P > 0.05), while the AUC, Cmax and CL had significant difference among the three groups after oral administration (P < 0.05). These results indicated that t1/2 and tmax did not vary with when apigenin was co-administered with raloxifene
Summary
Raloxifene is a selective estrogen receptor modulator (SERM) that produces both estrogenagonistic effects on bone and lipid metabolism and estrogen-antagonistic effects on the uterine endometrium and breast tissue. Because of its tissue selectivity, fewer side effects may be observed with the use of raloxifene as compared to first generation SERMs (e.g., tamoxifen). Some of the beneficial estrogenic effects of raloxifene include increasing bone mineral density and decreasing total and low-density lipoprotein cholesterol levels [1,2,3]. Raloxifene has already been approved by the U.S. Food and Drug Administration for the prevention of osteoporosis and breast cancer in high risk patients. It was reported that the bioavailability of raloxifen in rats was approximately 39% [4]. Raloxifene undergoes extensive biotransformation, but it does not appear to be metabolized by the cytochrome P450 pathway [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
