Comparison of effects of natural or artificial rodent diet on etoposide absorption in rats.
The oral administration of etoposide has erratic absorption and low bioavailability. P-glycoprotein (Pgp) located in the intestinal brush-border membrane may pump out orally absorbed etoposide and thus decrease etoposide's absorption. Since flavonoids are abundant in food, we speculated that the common natural rodent diet may contain some flavonoid-related constituents which influence etoposide absorption. We therefore compared the absorption of etoposide's in the everted gut sacs of rats pretreated for 30 minutes with two different diets, natural rodent diet or artificial rodent diet. The effect of quercetin, one of the plant derived flavonoids with Pgp modulating activity, on etoposide's absorption was also compared. The addition of natural rodent diet or quercetin increased etoposide's absorption in everted sacs of jejunum or ileum, in comparison to those added with artificial rodent diet. The enhancing effect of quercetin was compatible with the effect of natural rodent diet in the jejunum and was higher in the ileum. These in vitro data supported the hypothesis that certain dietary components, possibly flavonoid-related compounds, may influence Pgp's function in intestine and thus increase etoposide's absorption. However, when fed with natural rodent diet for one week, a lower enhancing effect on absorption was observed. This may be due to the metabolism of the ingredients with modulating activity to their inactive forms, thus reducing the effect of natural rodent diet on etoposide absorption. The results proved that feeding rats with natural or artificial rodent diet had no obvious effect on etoposide absorption in vivo.
Lo
Y L
YL
Department of Pharmacy, Chia-Nan College of Pharmacy and Science, Tainan Hsien, Taiwan, R.O.C.
Huang
J D
JD
D000042:Absorption; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000378:metabolism*; D004032:Diet; D005047:Etoposide / Q000008:administration & dosage / Q000378:metabolism*; D005526:Food, Formulated; D007082:Ileum / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D008297:Male; D011794:Quercetin / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D011794:Quercetin