Valacyclovir drug transport

Guo, A., Hu, P., Balimane, P., Leibach, F. H., Sinko, P. J., Interactions of a nonpeptidic drug, valacyclovir, with the human intestinal peptide transporter (hPePTl) expressed in a mammalian cell line,... 

Some drugs with low intrinsic permeability achieve acceptable oral bioavailability because they are substrates for uptake transporters, which normally function in nutrient uptake. The most prominent example is the peptide transporter, PepTl, which is active toward peptidomimetic antibiotics such as cephalexin, the antiviral agent valacyclovir [24] and other drugs. PepTl is natively expressed in Caco-2 cells, and adenovirus transduction has been used to increase PepTl expression levels [25]. However, the expression of PepTl was not polarized in this system and this expressed system appears to be of limited value as an improved screening model. PepTl has also been expressed in Chinese hamster ovary cells and a variety of other mammalian systems [26, 27]. 

Human PepTl was initially cloned from intestine (92) and was found to be localized to the brush border of intestinal epithelial cells (93) and in SI segment of apical proximal tubules (94). PepTl transports (3-lactam antibiotics (95), antiviral drugs such as valacyclovir and valganciclovir (96), and the angiotensin converting enzyme inhibitor captopril (97). Polymorphisms have been reported, however little is known regarding their functional consequences (64). 

Balimane P, Sinko P (2000), Effect of ionization on the variable uptake of valacyclovir via the human intestinal peptide transporter (hPepTl) in CHO cells. Biopharm Drug Dispos 21 165-174... 

Uptake transporter prodrug substrates have been used to improve drug absorption through GI tract. The most successful example is an antiviral prodrug valacyclovir, which shows oral bioavailability three to live times greater than its parent drug acyclovir (Weller et al., 1993). The increased oral bioavailability is attributed to PEPTl-mediated absorption, which was demonstrated by in situ rat perfusion model, Caco-2 cells, and PEPTl-transfected CHO cells (Balimane et al., 1998). 

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