Hydromorphone Pharmacokinetic-Pharmacodynamic Fingerprint
Information source: Northwestern University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pain; Ventilatory Depression
Intervention: hydromorphone (Drug)
Sponsored by: Northwestern University
Official(s) and/or principal investigator(s):
Dhanesh K. Gupta, M.D., Principal Investigator, Affiliation: Departments of Anesthesiology & Neurological Surgery, Northwestern University Feinberg School of Medicine
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.
Official title: A Hydromorphone High Resolution Pharmacokinetic-Pharmacodynamic Fingerprint as the Basis for Identifying Sex Differences in Opioid Pharmacokinetics and Pharmacodynamics
Study design: Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Opioid induced analgesia
Opioid induced ventilatory depression
Opioid induced miosis
Opioid induced EEG changes
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.
Minimum age: 21 Years.
Maximum age: 30 Years.
- 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.)
- 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
Locations and Contacts
Northwestern Memorial Hospital, Chicago, Illinois 60611, United States
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Starting date: January 2015
Last updated: April 21, 2015