The Prime Directive had to at least come up in conversation when first contact with the "Private Little War" natives was discussed. They definitely were a pre warp civilization.
Conversely, since the PD was not
mentioned, we might just as well deduce that it has absolutely nothing to do with the pre-warp or post-warp status of civilizations. After all, nowhere
in TOS was such a connection actually suggested.
PD is utterly unenforcable, except with respect to Starfleet personnel
Which is not a problem. It's a Starfleet regulation, so let it affect Starfleet only. TOS doesn't indicate it would be in place to protect natives from exposure - the only insight into why it exists is "The Apple" where it is to keep Starfleet from collapsing the governments or lifestyles of natives, regardless of their level of technology or exposure to the interstellar community. Essentially, it's a simple "Starfleet can't play God, even though it would be so ridiculously easy" rule to keep starship captains from misusing their powers.