Influence of concurrent and staggered dosing of semi-solid nutrients on the pharmacokinetics of orally administered carbamazepine in rats.

In the present study, we examined the effects of concurrent and staggered dosing of PG-soft ace-MP TM (PG), novel semi-solid enteral nutrients, on the pharmacokinetics of orally administered carbamazepine (CBZ) in rats due to the high possibility of drug interaction during the absorption process. The pharmacokinetic behavior of CBZ was considerably altered when administered concurrently with PG. The maximum serum CBZ concentration (Cmax) significantly decreased and the mean residence time (MRT) significantly increased. The elimination constant (ke) also significantly increased, but there were no significant changes in the area under the serum CBZ concentration versus time curve (AUC) and the time to reach Cmax (Tmax). However, these changes in the pharmacokinetic parameters were eliminated by waiting 20 min, the time interval equivalent to the Tmax described above, between CBZ administration and PG dosing. This study suggested that PG interferes with CBZ absorption from the digestive tract, although staggered administration of CBZ and PG prevented their interaction.

Downregulation of organic cation transporter 1 and breast cancer resistance protein with the induction of Pregnane X receptor in rat kidney impaired by doxorubicin.

Transporters expressed in the kidney play an important role in the excretion of endogenous substances and chemical drugs. The Pregnane X receptor (PXR) has been reported to be involved in regulating the expression of numerous transporters. In the present study, we examined the alteration in expression level of PXR, organic cation transporter 1 (OCT1) and breast cancer resistance protein (BCRP) in renal cell lines of rat origin and the kidney of rats when damaged by doxorubicin (DOX). The expression level of PXR in renal tubular epithelium NRK-52E cells was significantly increased by DOX at a concentration confirmed to cause cellular damage. The expression levels of OCT1 and BCRP were significantly lower in the DOX-treated cells than in the untreated cells. In model rats with DOX-induced nephrotoxicity, the alterations in renal expression of PXR, OCT1 and BCRP were similar to those in NRK-52E cells, although there was a difference in the degree of the changes.