The transport of antifolate aminopterin by human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8) was characterized using Xenopus laevis oocytes and was compared with that of methotrexate. Although hOAT1 and hOAT3 transported both aminopterin and methotrexate, uptake of methotrexate was greater in hOAT3-expressing oocytes than in hOAT1-expressing oocytes, and aminopterin was transported by hOAT1 more efficiently. The apparent 50% inhibitory concentration (IC₅₀) of aminopterin for p-aminohippurate uptake by hOAT1 was lower than that of methotrexate (methotrexate: 998 μM, aminopterin: 160 μM). On the other hand, IC₅₀ values of these antifolates for estrone sulfate transport by hOAT3 were comparable (methotrexate: 61.5 μM, aminopterin: 59.2 μM). The Michaelis-Menten constant and maximum velocity of aminopterin transport by hOAT1 were calculated to be 226 μM and 72.5 pmol/ oocyte/2 hr, respectively. Probenecid and non-steroidal anti-inflammatory drugs strongly inhibited the transport. These findings show that both aminopterin and methotrexate are substrates of hOAT1 and hOAT3, and that there are differences between the antifolates in terms of their transport characteristics.

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