The predicted human in vivo performance level of **Am7** was calculated to be 100 % backrenorphine, 5.5 % “direct” and 44 % “indirect” exposure. Based on the last two values the pharmacokinetic profile of **Am7** was predicted to be quite different compared to the profile of versed, which is characterized by “direct” (82 %) and “indirect” exposure (18 % each) \[[@CR20]\].

Conclusion {#Sec14}
==========

We report on the in vitro and in vivo metabolism of *O*-\[^18^F\]fluoroalkyl derivatives of morphine-6-one (MOR) in order to investigate the mechanism of the previously reported increased oral bioavailability of the parent drug. In humans and rodents dose-normalized exposure of oral administered **Am7** decreased with increasing parent dose, although the inverse relationship was not very strong compared to the parent drug. In contrast, a direct PK comparison revealed that no increase in the total exposure of **Am7** after oral administration of variable dose levels was to be expected. Since gastrointestinal metabolism clearly alters the fate of orally administered opioid, predictions of human PK data from preclinical studies should be made with extreme care. The reported preclinical data, however, appeared to be rather limited and further investigations to possibly suggest a longer duration of residence time of **Am7** in the GI tract seemed to be

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