Pharmacokinetic, Pharmacodynamic and Pharmacogenetic of Morphine After Surgery
Information source: Assistance Publique - Hôpitaux de Paris
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Orthopaedic Surgery
Intervention: intravenous morphine titration (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Assistance Publique - Hôpitaux de Paris Official(s) and/or principal investigator(s):
Frederic Aubrun, MD, PhD, Principal Investigator, Affiliation: Assistance Publique - Hôpitaux de Paris
Overall contact:
Frederic AUBRUN, MD PhD, Email: frederic.aubrun@psl.aphp.fr
Summary
The main objective of this study is to improve our knowledge on the pharmacodynamic,
pharmacokinetic, and pharmacogenetic relationships of morphine administered to relief severe
postoperative pain. The analysis will encompass the efficacy (acute during titration and
subacute during the first 24 hours) and adverse effects of morphine. Our purpose is also to
better characterize the age- and sex-related differences which probably markedly differ
between the two periods (acute vs sub acute).
Clinical Details
Official title: Assessment of the Pharmacokinetic, Pharmacodynamic, Pharmacogenetic Relationships of Morphine and Metabolites After Severe Postoperative Pain in Adults
Study design: Other, Cross-Sectional
Primary outcome: To improve our knowledge on the pharmacodynamic, pharmacokinetic and pharmacogenetic relationships of morphine administered after severe postoperative pain.
Secondary outcome: - Relationships between morphine consumption, clinical events (efficacy or adverse effects) and morphine (and metabolites) blood concentrations. Immediate postoperative period (PACU)- Relationships between clinical events (pain relief, failure in pain relief, adverse effects) and genetic polymorphism. - Relationships between sub-acute clinical events and PK/PG profile. (on the wards at 24 hours after surgery) To better characterize the age- and sex-related differences which differ between acute and sub-acute periods.
Detailed description:
No previous study attempted to characterize the pharmacodynamic, pharmacokinetic, and
pharmacogenetic relationships of morphine in the early postoperative period, whereas it is
the main clinical situation for severe pain and a unique model for its study (not possible
in the healthy volunteer). Indeed, intravenous titration of morphine is the first step for
pain control in the postanesthesia care unit. Administration of intravenous boluses of
morphine enables to obtain complete pain relief in 98% of the patients. We intend to study
the effects of morphine (intravenous titration then patient-controlled intravenous
administration (PCA) for 24 hours), perform dosages of plasma concentration of morphine an
its main metabolites, and also study gene polymorphisms coding for main proteins involved in
the pharmacokinetic and pharmacodynamic profile of morphine (hepatic metabolism,
distribution and elimination, interaction with morphine receptor). Five hundred patients
scheduled for major orthopedic surgery will be included in this prospective study. The main
objective of this study is to improve our knowledge on the pharmacodynamic, pharmacokinetic,
and pharmacogenetic relationships of morphine administered to relief severe postoperative
pain. The analysis will encompass the efficacy (acute during titration and subacute during
the first 24 hours) and adverse effects of morphine. Our purpose is also to better
characterize the age- and sex-related differences which probably markedly differ between the
two periods (acute vs subacute). We consider that this knowledge is important to confirm or
not several important concepts currently used to define the appropriate analgesic regimen to
control severe pain in the postoperative period.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion criteria :
- scheduled major orthopedic surgery
- spine, hip or knee surgery
- Body weight between 50 and 100 kg
- Caucasians
- ASA status 1 to 3
- no cognitive dysfunction
Exclusion criteria :
- allergy or contraindication to morphine
- renal impairment (Cr Cl < 30 ml/min)
- severe hepatic impairment
- surgery performed under regional anaesthesia
- preoperative treatment including strong or weak opioids
- pregnancy, patients under 18 years, addiction
Locations and Contacts
Frederic AUBRUN, MD PhD, Email: frederic.aubrun@psl.aphp.fr
Hopital de la Pitié Salpêtrière, Paris 75013, France; Recruiting
Frederic Aubrun, MD, PhD, Phone: +33() 1 42 16 22 59, Email: frederic.aubrun@psl.aphp.fr
Additional Information
Starting date: September 2006
Ending date: January 2010
Last updated: January 13, 2009
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