Disposition of Intravenous Ketorolac

Disposition of Intravenous Ketorolac After Cesarean Section

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

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Ketorolac Tromethamine

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• signed informed written consent
• pregnant women to whom ketorolac is administered by intravenous route for clinical indications
• preferable availability for revision in 6-12 weeks after delivery (around routine post-delivery check-up).

Exclusion Criteria:

• withdrawal of informed written consent
• known NSAID's intolerance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ketorolac; Ketorolac will be given to all patients as a part of routine medical care	Drug: Ketorolac Tromethamine; 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 Names: Taradyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ketorolac disposition following intravenous administration right after caesarean section	PK (concentration/time profile, protein binding, metabolism) and its covariates	up to 8 hours after first dose administration

Secondary Outcome Measures

Outcome Measure	Time Frame
optimalisation of ketorolac dose regimen during pregnancy and labor	up to 8 hours after first dose administration

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Karel Allegaert, MD PhD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Kulo A, Hendrickx S, de Hoon J, Mulabegovic N, van Calsteren K, Verbesselt R, Allegaert K. The impact of pregnancy on urinary ketorolac metabolites after single intravenous bolus. Eur J Drug Metab Pharmacokinet. 2013 Mar;38(1):1-4. doi: 10.1007/s13318-012-0108-7. Epub 2012 Nov 21.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: February 1, 2011
• First Submitted That Met QC Criteria: February 7, 2011
• First Posted (Estimate): February 8, 2011

Study Record Updates

• Last Update Posted (Estimate): December 13, 2011
• Last Update Submitted That Met QC Criteria: December 12, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: pain; pregnancy; ketorolac; non-pregnant state
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: 3214; 2011-000367-27 (EudraCT Number)