title: The impact of pregnancy on urinary ketorolac metabolites after single intravenous bolus.
abstract: Compared to female volunteers or postpartum, ketorolac clearance is higher at delivery. To explore the alterations that explain this higher clearance, urinary ketorolac metabolites collected at delivery (n = 40) were compared to female volunteers (unpaired, n = 8) or postpartum (paired, n = 8) following intravenous administration of 30 mg ketorolac tromethamine. A mean 38 (SD 9) % of the ketorolac dose was retrieved in 8-h urine collections. This was based on mean portions of 56 (20), 10 (14) and 33 (12) % for free ketorolac, ketorolac-glucuronide and p-hydroxy-ketorolac, respectively. The mean ketorolac-glucuronide portion at delivery (5 %) was lower compared to female volunteers (21 %) or postpartum (21 %) (p = 0.003 and p = 0.002, respectively). Similarly, there was a difference in mean portion of free urinary ketorolac at delivery when compared to healthy female volunteers (60-45 %, p = 0.046). Using paired statistics, the mean portion of total urinary ketorolac was lower (62-73 %, p = 0.015) while the portion retrieved as p-hydroxy-ketorolac was significantly higher at delivery compared to postpartum (38-28 %, p = 0.031). The differences in urine metabolites suggest that the increased ketorolac clearance at delivery is in part explained by increased metabolic clearance to p-hydroxy-ketorolac, reflecting increased oxidation activity.
authors.affiliation: Center for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Aida
authors.initials: A
authors.lastname: Kulo
authors.forename: Sarah
authors.initials: S
authors.lastname: Hendrickx
authors.forename: Jan
authors.initials: J
authors.lastname: de Hoon
authors.forename: Nedzad
authors.initials: N
authors.lastname: Mulabegovic
authors.forename: Kristel
authors.initials: K
authors.lastname: van Calsteren
authors.forename: Rene
authors.initials: R
authors.lastname: Verbesselt
authors.forename: Karel
authors.initials: K
authors.lastname: Allegaert
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine*; D001530:Belgium; D001711:Biotransformation; D016022:Case-Control Studies; D036861:Delivery, Obstetric; D005260:Female; D020719:Glucuronides / Q000652:urine; D006801:Humans; D006900:Hydroxylation; D007275:Injections, Intravenous; D020911:Ketorolac Tromethamine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000652:urine*; D008657:Metabolic Clearance Rate; D049590:Postpartum Period / Q000652:urine; D011247:Pregnancy; D014046:Tolmetin / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020719:Glucuronides; C059504:4-hydroxyketorolac; D020911:Ketorolac Tromethamine; D014046:Tolmetin