The advice from my Dad was to keep them at 40mph, although he drove Heinkel's (owned by Peter Green)and his own Messershcmitt KR200. They toured France in the KR200 and only suffered a broken throttle slide spring (fixed with a large washer bridging the two pieces), and drove the Heinkel to Gibraltar and back the following year over a two week period (all the annual leave you got back then). No major mechanical problems, apart from a bent track rod and worn tyre- Peter took a turn a bit too quick and put the car in a ditch whilst driving through Spain.
The following year Peter took a trip to Germany with his brother, and the Heinkel. During the trip the gearbox couldn't get fourth gear. They ragged the engine in third, and it went bang. Stranded in Germany they ordered up a complete new engine and gearbox from Stuttgart. Apparently they fell on their feet whilst waiting for the items to arrive,as a couple of frau's put them up, and I think they got more than bed and breakfast if you get my drift!
My Dad almost owned an Isetta, a shiny red one he saw in a dealer in Finchley, but it was a bit more than he could afford at the time, as it was only a year old, whereas his KR200 was a 1955 model, which I think cost him 75 quid in 1963.
Owners that drove Isetta's over long distances and high mileages like Vic Locke and Brian Westoby also said 40mph cruise, with the occasional burst up to 45mph. I think it was Brian that got over 200000 miles out of his Isetta engine before it needed major work, so that kind of proves the point that these engines will last if you don't belt the guts out of them.
Even at 40 mph the engine is working fairly hard. The bubbles would have benefited enormously from an extra gear or two, but I guess for the roads of the day, they were considered adequate.