title: Ketorolac effectively inhibits ureteral contractility in vitro.
abstract: BACKGROUND
  The use of ketorolac in the management of painful symptoms associated with urinary stones is well supported in the literature; however, the gastric and renal adverse effects limit the dose and duration of administration. As a nonselective cyclooxygenase inhibitor, ketorolac can act locally to help control renal colic by inhibiting smooth muscle contractions and inflammation. We sought to confirm ketorolac's inhibition of ureteral contractility and determine a dose response relationship to identify an effectiveness range.
  
  
  METHODS
  Porcine ureter strips attached to force displacement transducers were suspended in organ tissue baths that contained aerated Krebs buffer. Tissues equilibrated for 1 hour, and a spontaneous contractility rate was established. Tissues were incubated with a concentration-response curve of ketorolac (0.1 nM-10 microM) for 90 minutes and compared with indomethacin (1 muM) and dimethyl sulfoxide (DMSO) 0.1%. Contractility rates were recorded on a polygraph and analyzed for changes over exposure time.
  
  
  RESULTS
  Ketorolac inhibition of ureteral contractility was dose dependent. At 90 minutes, the average percent decrease from the spontaneous contraction rate for 0.1 nM ketorolac was 18.2%; 1 nM, 34.3%; 10 nM, 56.0%; 100 nM, 69.9%; 1 microM, 88.7%; and 10 microM, 98.3%. Ureteral contractility was significantly reduced by 1 microM ketorolac (39.0%; P = 0.016) at 15 minutes when compared with DMSO. In addition, 1 microM ketorolac was not significantly different at any time point from any of the higher doses studied.
  
  
  CONCLUSIONS
  Ketorolac inhibition of stretch-induced ureteral contractility is concentration-dependent between 1 nM and 1 microM. Local administration of ketorolac at these doses may be useful during the management of stones while at the same time limiting the risk for adverse effects.
authors.affiliation: Division of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: C Charles
authors.initials: CC
authors.lastname: Wen
authors.forename: Tawnya L Cary
authors.initials: TL
authors.lastname: Coyle
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Jerde
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Nakada
mesh_terms: D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D020910:Ketorolac / Q000008:administration & dosage / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D013552:Swine; D014513:Ureter / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin; D020910:Ketorolac