Renal handling of indomethacin: isolated membrane vesicles of proximal tubular cells as an in vitro model system for transport.

: The indomethacin-transport properties of luminal and contraluminal membrane vesicles derived from dog renal proximal tubular cells were studied. In both membranes saturable sodium gradient-dependent transport of indomethacin, sensitive to probenecid, was observed. In luminal membrane vesicles uptake occurred predominantly by passive facilitated diffusion, whereas in contraluminal membrane vesicles, uptake was based upon both passive simple diffusion and active concentrative transport. As a result, indomethacin may accumulate in vivo in the tubular cells thereby exerting a direct nephrotoxic effect.