title: Novel p38α mitogen-activated protein kinase inhibitor shows analgesic efficacy in acute postsurgical dental pain.
abstract: SCIO-469 is a selective p38α mitogen-activated protein kinase (MAPK) inhibitor for preclinical models of acute pain. This prospective, double-blind, randomized clinical study compared efficacy and safety of oral SCIO-469, ibuprofen, and placebo in postsurgical dental pain. Subjects (n = 263) undergoing extraction of 1 or more impacted mandibular third molars received preoperative treatment with SCIO-469 (150, 210, or 300 mg), ibuprofen (400 mg), or placebo; the 210-mg group received 90 mg postoperatively. A 4-point categorical scale and a 100-mm visual analogue scale were used to measure pain intensity. The primary end point was median time from first incision to first rescue medication using the Kaplan-Meier product limit estimator. All SCIO-469 groups had significantly longer times to rescue medication compared with placebo; preoperative and postoperative treatment with 210 + 90 mg SCIO-469 resulted in 8.1 hours versus 4.1 hours to rescue for placebo (P = .003). Ibuprofen also increased time to rescue medication (6.6 hours) versus placebo (P = .04). Dizziness, headache, and nausea were the most frequently reported adverse events. This is the first clinical demonstration of antinociceptive effects in acute pain with preoperative administration of a p38α MAPK inhibitor.
authors.affiliation: Scios Inc, Mountain View, CA, USA. Sandra_tong@affymax.com
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Tong
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Daniels
authors.forename: Peter
authors.initials: P
authors.lastname: Black
authors.forename: Stephen
authors.initials: S
authors.lastname: Chang
authors.forename: Andrew
authors.initials: A
authors.lastname: Protter
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Desjardins
mesh_terms: D059787:Acute Pain / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008964:Molar, Third / Q000601:surgery*; D010147:Pain Measurement; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D014081:Tooth Extraction / Q000009:adverse effects*; D014095:Tooth, Impacted / Q000601:surgery*; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D000700:Analgesics; D007211:Indoles; D047428:Protein Kinase Inhibitors; C499748:SCIO-469; D048308:Mitogen-Activated Protein Kinase 14; D007052:Ibuprofen