Influence of UGT2B7, CYP3A4, and OPRM1 Gene Polymorphisms on Transdermal Buprenorphine Pain Control in Patients with Critical Lower Limb Ischemia Awaiting Revascularization

• Published in: Pain practice 2016-09, Vol.16 (7), p.842-849
• Main Authors: Blanco, Francisco, Muriel, Clemente, Labrador, Jorge, Gonzalez-Porras, Jose R., Gonzalez-Sarmiento, Rogelio, Lozano, Francisco S.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Adult; Analgesics, Opioid - administration & dosage; buprenorphine; Buprenorphine - administration & dosage; critical limb ischemia; CYP3A4; Cytochrome P-450 CYP3A - genetics; Female; genetics; Glucuronosyltransferase - genetics; Humans; Ischemia - complications; Lower Extremity - blood supply; Male; Middle Aged; OPRM1; pain; Pain - drug therapy; Pain - etiology; Pain - genetics; Pain Management - methods; Pain Measurement; peripheral arterial disease; polymorphism; Polymorphism, Single Nucleotide; Receptors, Opioid, mu - genetics; transdermal; UGT2B7
• ISSN: 1530-7085; 1533-2500
• DOI: 10.1111/papr.12343

Background Pain control in critical limb ischemia (CLI) varies considerably between individuals. Objective To evaluate pharmacogenetically the response to transdermal buprenorphine (BUP‐TTS) in patients with CLI who are awaiting revascularization. Methods One hundred and seven patients with CLI were treated with BUP‐TTS. The following were analyzed: (1) pain perception (visual analog scale (VAS) before and 4 days after treatment) and (2) genetics: glucuronosyltransferase (UGT2B7), cytochrome (CYP3A4), and μ‐opioid receptor (OPRM1) gene polymorphisms. Results Ninety‐three patients completed the study. The VAS score by the fourth day of analgesia dropped from 6.82 to 3.38 (P < 0.05). The analgesic response to BUP‐TTS was greater in men than in women (P = 0.019). Patients who were AA homozygotes for the CYP3A4 gene showed the best response to analgesic treatment (P = 0.003). The combination of the CYP3A4 gene with UGT2B7 or OPRM1 was favorable to the effect of the CYP3A4 gene (P = 0.045 and P = 0.026, respectively). The combination of UGT2B7 with OPRM1 was ineffective (P = 0.648). The 3 polymorphisms together had no effect on response to treatment (P = 0.461). Conclusions BUP‐TTS is efficacious in the control of pain in patients with CLI. The homozygous AA carriers of the CYP3A4 gene respond better to treatment with BUP‐TTS.