use a router with a flush trim bit.
remove the lexan, drill the hole in the wood/mdf to the size you want it, then put the lexan back on, and use a flush trim router bit to cut the lexan using the hole in the wood as the guide.
i see you are not sure if it is lexan or plexiglass, i haven't personally used lexan, but i can tell you i've done this alot with plexiglass and it works beautifully, the router cuts through the plexi like a hot knife through butter.