I have some info that may be helpful.
I have owned 3 different .416 Weatherby's, a .416 Remington several .458's and a .460 and also have several decades handloading experience as well as many many hundreds of kills using these same cartridges.
I think you should go with the .416 Remington.
The reason the .375 is universally popular is not because of it's power or killing ability on large game, but because it has a recoil level that most casual hunters and that is really what most of us are, can accommodate.
We already knew that putting a bullet in the right place is the primary objective, so if it is a .375 caliber bullet then usually everyone is happy and you get a taxidermy bill.
The .416 hits noticeably harder than the .375 but the difference in recoil does not take it into an area that you will not be able to handle. It is more, make no mistake, but if you load the cartridge to your recoil tollerance and practice as you should, then it will prove more effective and comforting on dangerous game.
For lion, I recommend you use the Woodleigh Weldcore 340 grain spire point bullet and go for accuracy as you will have confidence to place shots precisely both for plains game and for lion.
For a heavy load, you can go 2 roads and I would get a box of each to see what your rifle likes and make sure you are still ok with the loads in terms of recoil.
Buy a box of 350 Grain Barnes X bullets and a box of the new Woodleigh 450 Grain Weldcores with the heavier jackets.
Woodleigh is no "johnny come lately" like the sudden rush of bonded bullets on the market today and Woodleigh's are tested on buffalo before being released to the public so they are always a proven bullet.
The 350 X is a great bullet for longer shots and will penetrate a buffalo lengthwise. The Woodleigh will introduce him to the speed of gravity with certainty and haste. Woodleigh bullets absolutely numb big animals and take away all their enthusiasm for aggression.
I personally, would take all these to Africa but I would base the loads I carried in the field on terrain which will influence the range of the shot. Your outfitter can advise you on that.
Regarding the 45's, the other contributors are correct as to the increase in recoil and only hardened shooters can conquer these rifles.
In terms of performance on game, my experiecne is that the .458 is a much better cartridge than the experts claim, especially when handloaded to potential. I use 2 loads in my current .458 and I use the same bullets in my .460.
These are the 400 grain Barnes X and the 550 grain Woodleigh. My experievce with these 2 bullets is that if it can breath, these bullets will cure the problem permanently.
I load the 400 grainers to 2440 fps in the .458 which is a top velocity load and to 2900 fps in the .460 which makes it think it is a 7mm Remmy.
With the 550 grainers, I get 2050 fps in the .458 with very heavy recoil because of the light weight of the Model 70 and 2460 fps in the .460.
Either load slams one ton animals to the ground. The .45's do hit harder than the .416's there is no challenging that fact. What is enough is really determined by what is enough for you as an individual to handle.
Being a handloader is the most practical thing you can do to ensure you end up with the best combination.
