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Hydromorphone Pharmacokinetic-Pharmacodynamic Fingerprint

Information source: Northwestern University
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pain; Ventilatory Depression

Intervention: hydromorphone (Drug)

Phase: N/A

Status: Recruiting

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

Overall contact:
Dhanesh K Gupta, M.D., Phone: 312-926-8369, Email: dkgupta.northwestern@gmail.com

Summary

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.

Clinical Details

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Opioid induced analgesia

Opioid induced miosis

Opioid induced EEG changes

Secondary outcome: Opioid induced ventilatory depression

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.

Eligibility

Minimum age: 21 Years. Maximum age: 30 Years. Gender(s): Both.

Criteria:

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

Locations and Contacts

Dhanesh K Gupta, M.D., Phone: 312-926-8369, Email: dkgupta.northwestern@gmail.com

Northwestern Memorial Hospital, Chicago, Illinois 60611, United States; Recruiting
Dhanesh K Gupta, M.D., Principal Investigator
Additional Information

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Starting date: May 2010
Last updated: January 5, 2011

Page last updated: December 08, 2011

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