It's certainly possible. The early 4.0 was available (though rare) with a manual R380 and everything can be retrofitted to a 4.6. But it will be a lot of work. To begin with, you need to replace the pedalbox and rewire or replace the ECU for the transferbox, as it takes a signal from the autobox XYZ-switch. I considered it, but decided to look for a manual 4.0 instead and swap the engines, as that's a lot less work/trouble. Looking to put a 5.0 in in the near future. I'm sure the R380 will stand up to it, given a minimum of mechanical sympathy.
It's not impossible, just needs the right combination of bellhousing, transfer box input shaft and some mods to the electrics BUT, if you're looking to use the R380 manual box the 4.6, in standard trim puts out 380Nm of torque which is on the limit of the R380 (rated to max 380Nm). In addition, the standard manual clutch setup won't handle that kind of torque. It slips at around 320Nm.
An uprated clutch is a wise choice, but no need to worry about the R380. I've driven one with a mildly tuned 4.6 for several years. And I'm confident enough to put a R380 behind the 5.0 V8 I'm planning to build.