The low oral bioavailability of BUP increases the risk of highly variable pharmacokinetics since drugs with low bioavailability are often subject to high inter-individual differences, drug-drug interactions (Fihlman et al., 2018), and food effects (Maharao et al., 2017)), and may also increase safety risks, since norbuprenorphine shows 10 fold higher respiratory depression than BUP (Strang et al., 2018). This evidence concerns the gene COMMD3 and Respiratory insufficiency due to muscle weakness.