Mechanism of acyclovir uptake in rat jejunum.

The intestinal uptake mechanism of the purine analogue, acyclovir, was investigated in rat jejunum using in vitro and in situ methods. The pyrimidine, uracil, was used as a reference compound for carrier-mediated transport, while the purine analogue, caffeine, served as the reference compound for passive diffusion. With the in vitro intestinal ring method, acyclovir uptake was linear in the concentration range 0.01-5 mM. No significant competition for uptake was observed with uracil, 6-mercaptopurine, hypoxanthine, caffeine, or adenine. In addition, use of 2,4-dinitrophenol (DNP), ouabain, or K+ substituted buffer did not reduce the rate of acyclovir uptake. The in situ single-pass perfusion method yielded a wall permeability of approximately 0.2, which did not vary consistently with increasing concentration. Coperfusion of acyclovir with DNP did not decrease the wall permeability. None of the data provided evidence of a carrier-mediated transport system, and it was concluded that the uptake mechanism of acyclovir in the rat jejunum is predominantly via passive diffusion.