Transport of the anti-varicella-zoster virus agent 6-methoxypurine arabinoside and its 2'-O-valerate prodrug into human erythrocytes.

The transport of the anti-varicella-zoster virus agent 6-methoxypurine arabinoside and its 2'-O-valerate prodrug, 170U88, was investigated by using the human erythrocyte model. The influx of 6-methoxypurine arabinoside was found to occur primarily by means of the nucleoside transporter. (i) Influx was nonconcentrative and saturable (Km = 106 +/- 2 microM). (ii) The inhibitors of nucleoside transport, nitrobenzylthionosine, dipyridamole, and dilazep, inhibited the influx of 10 microM 6-methoxypurine arabinoside by greater than 94%. (iii) Influx was inhibited by nucleosides but not by nucleobases. (iv) 6-Methoxypurine arabinoside was a competitive inhibitor (Ki = 129 +/- 10 microM) of adenosine influx, and adenosine (Km = 160 +/- 9 microM) was found to be a competitive inhibitor (Ki = 134 +/- 9 microM) of 6-methoxypurine arabinoside influx. By contrast, the influx of 170U88 occurred by means of nonfacilitated diffusion. (i) Influx was linearly dependent on the 170U88 concentration. (ii) Influx was not inhibited by nucleobases, nucleosides, or inhibitors of nucleoside transport.