Furthermore, patients homozygous for the minor TT allele of the ABCB1 gene experienced more opioid-related side effects such as sweating, muscular tension, stress and sedation than patients with the major CC/CT alleles. This is in agreement with other studies indicating an increased risk of opioid-induced side effects [54], such as early respiratory depression with fentanyl treatment [55]. It has been proposed that this effect involves impairment of P-glycoprotein transport, resulting in higher brain concentrations of the substrate (e.g. remifentanil). However, earlier studies have indicated decreased effects of methadone in patients with the minor TT allele [13,56] and a smaller increase in R-methadone levels with quetiapine [57]. The consequence of this mutation in the ABCB1 gene may be related to the effectiveness of the transporter P-glycoprotein, encoded by this gene. The transporter P-glycoprotein, is thus known to act on a broad range of prescription medicines, including opioids. The ABCB1_3435C>T SNP has been associated with mRNA, protein and serum levels, and with responses to a number of medical drugs [58].
