Pharmacokinetics of Multiple-Dose Methadone in Children

Determining the pharmacokinetics of multiple-dose methadone for the treatment of opioid withdrawal in children.

Summary

Critically ill children routinely receive opioids for analgesia and sedation with the goals of reducing pain and stress, facilitating ventilation, and avoiding secondary complications. Continuous infusions of opioids can induce tolerance, however, sometimes resulting in withdrawal symptoms if the drugs are discontinued abruptly. In fact, opioid withdrawal is a major problem in the pediatric intensive care unit, where it is estimated to occur in up to 57% of patients. Withdrawal symptoms are not only unpleasant but can be life-threatening and may prolong the need for hospitalization.

Fortunately, gradual opioid tapering is possible with drugs such as methadone, which can be substituted for narcotic infusions during the weaning process to prevent withdrawal symptoms. Methadone is an opiate commonly prescribed to hospitalized children, particularly in younger age groups. We know that methadone levels in the blood vary dramatically in adults, especially after oral administration. That is likely to be the case in children, but there are virtually no studies to guide dosing in children. The methadone product label currently states that safety and effectiveness in patients below the age of 18 years have not been established, and no dosing information is provided.

The primary objective of this prospective, multicenter, open-label, multiple-dose study is to determine the pharmacokinetics of enteral methadone in children treated for opiate withdrawal. The study population will include children aged >90 days to <18 years of age prescribed methadone per routine care. As many as 36 participants will be enrolled at up to 5 sites. Participation in the study will last up to 10 days (up to 5-day treatment period, up to 5-day observation period after study drug administration to monitor for adverse events and collect elimination samples).

OVERVIEW

Status:
Enrollment closed; analysis ongoing

ClinicalTrials.gov identifier:
NCT01945736

Principal Investigator:
Kevin Watt, MD
Duke Health, Durham, NC

NEWS

  • Methadone study enrolls first patient January 17, 2014 On January 10, 2014, the site team at the Medical University of South Carolina enrolled the first patient into the “Pharmacokinetics of Multiple-dose Methadone in Children” study. Andrew Atz, MD, principal investigator, Hibah Al Nasiri, study coordinator, and Patricia Infinger, research manager, oversee the team at this institution. This multicenter study will determine the pharmacokinetics of ...