Pharmacokinetics of Intranasal Ketorolac in Children

Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) that is typically given to both adults and children by the intravenous (IV) or intramuscular (IM) route for analgesic purposes. Ketorolac can also be given by the intranasal (IN) route using a mucosal atomization device (MAD). We aim to study the pharmacokinetics of ketorolac when administered by the IN route using the MAD.

Study Overview

• Status: Terminated
• Conditions: Pain; Evaluating Pharmacokinetics of Intranasal Ketorolac
• Intervention / Treatment: Drug: Ketorolac

Detailed Description

The intranasal (IN) route of administering medications is an effective means of delivering analgesics to children in a painless and minimally distressing manner, especially in comparison to traditional means of intravenous (IV) or intramuscular (IM) administration, which require a painful and distressing needle stick.

Ketorolac is an analgesic that is commonly administered to children, and can be given by the IN route, in addition to the IV and IM routes. However, the pharmacokinetics of intranasal ketorolac when administered in children has only been described in a limited fashion. The administration of IN ketorolac in children, using the proprietary SPRIX device, which atomizes a fixed amount of ketorolac, produces serum concentrations of ketorolac that are associated with analgesia. However, the concentrations of ketorolac achieved using a mucosal atomization device (MAD) has not yet been evaluated in children presenting to the emergency department. The MAD is a plastic device that attaches to the top of a syringe (see figure). The MAD is much more commonly used for atomizing medications; allows a variable dosage to be administered; and has been shown to be a means of effectively delivering other analgesics and sedatives intranasally.

The purpose of this study is to assess the pharmacokinetics of IN ketorolac when using a MAD to deliver the medication in children presenting to the emergency department. We will determine the maximum serum concentration achieved (Cmax), time to maximum serum concentration achieved (Tmax), and bioavailability (compared to IV ketorolac) when ketorolac is administered intranasally using a MAD.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York Presbyterian Morgan Stanley Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Present to the emergency department with a painful condition for which the treating physician decides to administer ketorolac as part of their usual care.

Exclusion Criteria:

• Known allergy to ketorolac
• Contraindication to receiving ketorolac
• Receiving any NSAID within the past 6 hours
• Presence of an intranasal obstruction that cannot be readily cleared using suction or nose-blowing
• Inability to speak English or Spanish
• Critical illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal ketorolac; Ketorolac 0.5 mg/kg, maximum single dose = 30 mg. Administered once by intranasal route using a mucosal atomization device.	Drug: Ketorolac; Non-steroidal anti-inflammatory drug; Other Names: Toradol
Active Comparator: Intravenous ketorolac; Ketorolac 0.5 mg/kg, maximum single dose = 30 mg. Administered once by intravenous route.	Drug: Ketorolac; Non-steroidal anti-inflammatory drug; Other Names: Toradol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of intranasal ketorolac	Maximum serum concentration of ketorolac, after intranasal administration	60 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax of intranasal ketorolac	Time to maximum serum concentration of ketorolac, after intranasal administration	6 hours
Bioavailability of intranasal ketorolac	Bioavailability of intranasal ketorolac; expressed as a percentage (numerator = serum levels achieved by intranasal administration, denominator = serum levels achieved by intravenous administration)	6 hours

Collaborators and Investigators

• Sponsor: Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): November 29, 2017
• Study Completion (Actual): November 29, 2017

Study Registration Dates

• First Submitted: November 14, 2014
• First Submitted That Met QC Criteria: November 19, 2014
• First Posted (Estimate): November 21, 2014

Study Record Updates

• Last Update Posted (Actual): January 17, 2019
• Last Update Submitted That Met QC Criteria: January 15, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Pediatric; Pharmacokinetics; Intranasal; Ketorolac
• Additional Relevant MeSH Terms: 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
• Other Study ID Numbers: AAAN5404