Disposition of Intravenous Ketorolac
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is:

        -  to document ketorolac disposition (concentration/time profile, protein binding,
           metabolism) and its covariates following intravenous (iv) administration of ketorolac
           right after caesarean section and to compare those observations (n=32) with non-pregnant
           state (n=8) (intra-subject PK comparison)

        -  to document biochemical tolerance of ketorolac

        -  to evaluate if optimalisation of ketorolac dose regimen during pregnancy and labor are
           appropriated and needed

        -  to quantify the neonatal exposure to ketorolac through excretion in the breast milk
    

Detailed description: 
      Prospective, single-center, open label study on the pharmacokinetics of intravenous (iv)
      ketorolac administration in pregnant women right after caesarean section. Patients will be
      included after signed informed consent. Ketorolac has been selected for this study as it is
      routinely administered for postoperative pain relief. At this stage, we only have the
      intention to document ketorolac pharmacokinetics and metabolism based on the dosing regimen
      as currently used in the clinical setting, and therefore will not interfere with either
      clinical indications, nor with dosing as prescribed by the attending physician. This drug is
      routinely administered (30 mg q8h) after caesarean section.

      Drug administration and collection of samples will be obtained to the current clinical and
      nursing standard procedures. After dilution in 50-100 ml bag of normal saline drug will be
      administered after caesarean section by iv bolus, through a peripherally inserted venous
      catheter, 30 mg, 3 times in one day. The intended duration of administration is 5-10 minutes.

      Blood samples will be collected (in heparinised tubes) according to following schedule: 1, 2,
      3, 4, 6 and 8 hours after iv administration, through a second peripherally inserted venous
      catheter dedicated for blood sampling only. Blood samples will be centrifuged immediately
      after collection and subsequently stored at -20 °C until analysis. Urine samples will also be
      collected, before drug administration in the first 8 hours after the first drug
      administration, through a bladder catheter in patients in whom a bladder catheter is
      available for clinical indications.

      In a subgroup of former patients (n=8), we plan to repeat this procedure 6-12 weeks after
      delivery (for intra-subject PK comparison). However, only a single iv ketorolac dose will be
      administered, and sampling will be limited to 6 samples up to 8 h following start of iv
      administration. A population pharmacokinetics approach will be used, hereby comparing the
      data on PK already reported in adults and the newly collected data following pregnancy.
    

Intervention name(s): Ketorolac Tromethamine
Intervention type(s): Drug
Intervention description(s): After dilution (solution for injection, 10 mg/1ml) in 50-100 ml bag of normal saline drug will be administered by iv bolus, through a peripherally inserted venous catheter, 30 mg, 3 times in one day. The intended duration of administration is 5-10 minutes.
Other intervention name(s): Taradyl
Intervention MeSH terms: Ketorolac; Ketorolac Tromethamine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ketorolac; pain; pregnancy; non-pregnant state