A very similar Km antibiotics value was obtained in hPEPT1/CHO cells and in rat and rabbit tissues and Caco-2 cells, suggesting that hPEPT1 dominates the intestinal transport properties of VACV in vitro. The purpose of this study was to characterize tenoretic dose the interaction of VACV and the human intestinal peptide transporter antibiotics using Chinese hamster ovary (CHO) cells that overexpress ciprofloxacin eye drops infants the human intestinal peptide transporter (hPEPT1) gene. Interactions of a nonpeptidic drug, Valacyclovir antibiotic ( Valtrex ), with the human intestinal peptide transporter (hPEPT1) expressed in a mammalian cell line.The results of previous work performed in our laboratory genital herpes using an in situ perfusion technique in rats and rabbit apical brush border membrane vesicles have suggested that the intestinal uptake of Valacyclovir ( Valtrex ) (VACV) appears to be mediated by multiple valtrex membrane transporters. Proton cotransport was not observed in hPEPT1/CHO cells, consistent with previously observed results in tissues and Caco-2 cells. VACV uptake was significantly greater in CHO cells transfected with hPEPT1 than in cells transfected genital herpes with only the vector, pcDNA3. Using these techniques, it is difficult to characterize the transport kinetics of VACV with each individual transporter in the presence of multiple known or unknown transporters. Also, the results demonstrate that the hPEPT1/CHO cell system has use in investigating the transport kinetics of drugs with the human intestinal peptide transporter hPEPT1; however, the extrapolation of these transport properties to the in vivo situation requires further investigation.. The present results demonstrate that VACV is a substrate for the human intestinal peptide transporter in hPEPT1/CHO cells and that although transport is pH dependent, proton cotransport is not apparent.
VACV uptake was markedly inhibited by various dipeptides and beta-lactam antibiotics, and Ki values of 12.8 /- 2.7 and 9.1 /- 1.2 mM were obtained for Gly-Sar and cefadroxil at pH 7.5, respectively. VACV uptake was concentration dependent and saturable with a Michaelis-Menten constant and maximum velocity of 1.64 /- 0.06 mM and 23.34 /- 0.36 nmol/mg protein/5 min, respectively. The optimum pH for VACV uptake was determined to occur at pH 7.5.
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