Effects of ketorolac tromethamine on erythropoietin levels in Sprague Dawley rats.
Ketorolac tromethamine (KT) is a potent analgesic, most often used in its injectable form postoperatively. Similar to other nonsteroidal antiinflammatory drugs (NSAIDs), it inhibits prostaglandin (PG) synthesis. Prostaglandins have been shown to be involved in the regulation of renal function as well as erythropoietin (Ep) production. The intent of this study was to determine the effect of KT on plasma Ep levels in Sprague Dawley (SD) rats. Twenty rats received either 15 mg/kg/d or the KT vehicle IM for 5d. Blood samples (1 ml) were collected via tail vein each day of treatment. Plasma Ep levels were significantly higher in the KT rats than normal controls with the greatest difference occurring on d4 of treatment (70.1 +/- 10.8 vs 30.9 +/- 10.84 mU/ml, p < 0.01). This change in Ep corresponded with a significant reduction in hematocrit (KT, 29.5 +/- 2.2 vs C, 40.8 +/- 2.2%, p < 0.01). Presence of fecal blood was noted in the KT treated rats. A similar second experiment was designed to determine if blood loss was the cause of altered Ep production. In this experiment controls (HC) were bled via tail vein, to match the hematocrits of KT treated animals. Repeated administration of KT led to a steady reduction in hematocrit. When compared, hematocrit matched animals showed no difference in plasma Ep levels on all days of treatment (KT, 48.0 +/- 4.9 vs HC, 44.6 +/- 3.1 mU/ml, N.S.). In conclusion, repeated administration of KT showed no impairment of Ep production and release in response to reduced hematocrit, suggesting that in this instance, prostaglandin inhibition plays a minimal role in Ep production or release.
Hoff
K K
KK
Department of Internal Medicine, University of South Dakota School of Medicine, Sioux Falls, USA.
Zawada
E T
ET
Alavi
F K
FK
Leyse
J W
JW
Santella
R N
RN
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006400:Hematocrit; D020911:Ketorolac Tromethamine; D009780:Occult Blood; D011453:Prostaglandins / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014046:Tolmetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014325:Tromethamine / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D011453:Prostaglandins; D014325:Tromethamine; D004921:Erythropoietin; D020911:Ketorolac Tromethamine; D014046:Tolmetin