Status:
COMPLETED
Methadone Pharmacokinetics and Cardiac Effects in Newborns
Lead Sponsor:
University of Utah
Collaborating Sponsors:
Case Western Reserve University
Children's Mercy Hospital Kansas City
Conditions:
Pain
Eligibility:
All Genders
29-48 years
Phase:
PHASE1
Brief Summary
The Primary objectives of this proposal are to determine the population kinetics for methadone and its enantiomers in preterm newborns and infants at 29 weeks to 48 weeks post menstrual age (PMA) who ...
Detailed Description
Painful procedures are frequent during the NICU care of sick newborns. Newborns are capable of perceiving pain by the time in fetal development when they reach our current limits of viability around 2...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA
- Patients must be in the NICU or PICU with continuous cardiorespiratory monitoring
- PMA between 29 0/7 to 48 6/7 weeks (EGA at birth (wks) + postnatal age wks) at the start of study
- Weight \>1499 gm at the time of enrollment
- Postnatal age of 3 days or more
- Arterial or venous catheter suitable for blood sampling with a separate i.v. infusion site is preferred, but not essential
- Currently being treated with methadone bolus doses or fentanyl or morphine in bolus doses or by infusion for clinical indications and expected to be treated for at least 1-2 more days with opioids for study of single dose pharmacokinetics and to be treated for 3-5 days more during the study of bioavailability
- Hematocrit ≥35%
- Parental permission
- Approval by the patient's attending physician
- Treatment Scheme 1, studied for 48 hr after a single i.v. dose of methadone
- Feeding or not feeding
- Mechanically ventilated
- Treatment Scheme 2 studied for 24 to 48 hr after a single i.v. dose of methadone AND again after a single enteral dose of methadone after the end of sampling after the first dose; order of doses is randomized. If the caregiver feels the patient is too sedated at the end of pK sampling after Dose, 1, then Dose 2 will be delayed until patient is judged to need analgesic treatment.
- Tolerating enteral feeding for 3 consecutive days before study
- EXCLUSION CRITERIA
- Clinically diagnosed liver dysfunction
- Clinically diagnosed kidney dysfunction with urine output \<1.0 ml/kg/hr
- Gastrointestinal malformation or dysfunction that might interfere with enteral drug absorption
- Congenital anomalies or other conditions thought to be incompatible with life
- History of arrhythmias, excluding bradycardia associated with apnea
- Unstable cardiorespiratory status
- Serum K+ \<3.0 mEq/L
- QTc\[H\] \>0.449 ms using Hodges correction =QT + 1.75(rate - 60).
- Family history of unexplained early cardiac deaths, syncope, or long QT syndrome in primary relatives: siblings, parents, grandparents, or aunts/uncles.
- Treatment with inhibitors and inducers of CYP3A4, CYP2B6, CYP2D6 and PGP including:
- amiodarone, carbamazepine, ciprofloxacin, clarithromycin, clotrimazole, dexamethasone, erythromycin, ethosuximide, fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, metronidazole, miconazole, nelfinavir, paroxetine, phenobarbital, phenytoin, quercetin, quinidine, rifabutin, rifampin, ritonavir, saquinavir, sulfadimidine, sulfinpyrazone, troleandomycin
Exclusion
Key Trial Info
Start Date :
October 1 2007
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
February 10 2017
Estimated Enrollment :
7 Patients enrolled
Trial Details
Trial ID
NCT00715988
Start Date
October 1 2007
End Date
February 10 2017
Last Update
June 1 2022
Active Locations (2)
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1
University of Utah
Salt Lake City, Utah, United States, 84108
2
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113