Hydromorphone Pharmacokinetic-Pharmacodynamic Fingerprint

April 21, 2015 updated by: Dhanesh Gupta, Northwestern University

A Hydromorphone High Resolution Pharmacokinetic-Pharmacodynamic Fingerprint as the Basis for Identifying Sex Differences in Opioid Pharmacokinetics and Pharmacodynamics

The primary objective of the proposed work is development of a high resolution pharmacokinetic-pharmacodynamic (PK-PD) model of hydromorphone for experimental pain stimuli, ventilatory depression, and surrogate biomarkers of opioid effect that will allow the fingerprinting of hydromorphone. This fingerprint will serve as the basis for the development of dosing strategies that efficiently maximize analgesia while minimizing ventilatory depression and sedation. For example, this high-resolution fingerprint will allow precise estimation of an initial hydromorphone target effect site concentration (Ce) from those of effectively administered synthetic opioids with previously determined high-resolution fingerprints (i.e., remifentanil or fentanyl), thereby minimizing underdosing of hydromorphone for analgesia and minimizing side effects.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

After 6 h of fasting, each volunteer will have a 20G arterial-line placed in the radial artery for early blood sampling and an 18 G peripheral intravenous catheter placed in the contralateral forearm for drug administration and later blood sampling. Continuously monitored vital signs will include ECG, invasive blood pressure, hemoglobin, O2 saturation, end-tidal CO2, and respiratory rate (from the capnogram) recorded.

After baseline PD data acquisition, a bolus of 0.2 mg/kg hydromorphone will be administered over 10 sec via the free-flowing peripheral IV (t=0) and 3 mL arterial blood samples will be obtained at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, and 2 min using a stop-cock and manifold system. Subsequent blood samples will be acquired at 3, 4, 5, 7.5, 10, 15, 20, 25, 30, and 45 min and 1, 1.25, 1.5, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 20, and 24 h. Although EEG will be acquired continuously, the remaining pharmacologic data will be recorded at discrete times s in the initial 5 min: pupillometry at 1, 2, and 5 min; ventilation at 2 min; temperature analgesia at 3 and 5 min, and sedation level at 4 min. This will allow the ventilation and pupillometry to be acquired in a resting state, thereby limiting distortion of these responses by stimulation. Subsequently, all data will be acquired at all PK time points in the following sequence - ventilation and EEG (simultaneously), pupillometry, modified OAA/S score, and temperature analgesia. After 2 h, once a pharmacologic parameter has returned to baseline for 2 sequential measurements, recording of that parameter will be stopped. During the study, if the volunteer is unable to use the device trigger, due to opioid-induced sedation, the tolerance level for increased temperature will be defined as the temperature at which the volunteer exhibits withdrawal movement of the tested limb. Once all data acquisition has been completed, the volunteer will be allowed to drink clear liquids. Subsequently, the diet will be advanced as tolerated. The volunteer will be monitored hourly (vital signs) in the Clinical Research Unit until all of the blood samples have been acquired.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 30 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • within 20% of their ideal body weight
  • 21-30 years old
  • ASA I (no systemic disease)
  • No history of PONV (except wisdom teeth extraction)
  • No long term medication use
  • No history of coagulation defect (i.e easy bruising, gum bleeding with teeth brushing, frequent nose bleeds, past documented coagulopathy, etc.)

Exclusion Criteria:

  • Inability to place an arterial line
  • A failed urine drug test on admission to the CRU
  • A positive pregnancy test on admission to the CRU
  • A hemoglobin level < 12.5 g/dL on admission to the CRU

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: hydromorphone
open label single arm pharmacokinetic-pharmacodynamic study
Drug: hydromorphone
hydromorphone 0.02 mg/kg
Other Names:
  • Dilaudid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Opioid induced analgesia
Time Frame: 24 hours
A combined PK-PD model for hydromorphone induced analgesia (heat pain tolerance) will be developed
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Opioid induced ventilatory depression
Time Frame: 24 hours
A combined PK-PD model for hydromorphone induced ventilatory depression will be created
24 hours
Opioid induced miosis
Time Frame: 24 hours
A combined PK-PD model for hydromorphone induced miosis will be developed
24 hours
Opioid induced EEG changes
Time Frame: 24 hours
A combined PK-PD model for hydromorphone induced EEG effects will be developed
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Investigators

  • Principal Investigator: Dhanesh K. Gupta, M.D., Departments of Anesthesiology & Neurological Surgery, Northwestern University Feinberg School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Actual)

January 1, 2015

Study Completion (Actual)

January 1, 2015

Study Registration Dates

First Submitted

May 10, 2010

First Submitted That Met QC Criteria

May 13, 2010

First Posted (Estimate)

May 14, 2010

Study Record Updates

Last Update Posted (Estimate)

April 22, 2015

Last Update Submitted That Met QC Criteria

April 21, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU00013543

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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