title: Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease.
abstract: Vaso-occlusive episodes (VOEs) are a significant source of morbidity among children and adults with sickle cell disease (SCD). There is little information on methadone use for SCD pain. This investigation evaluated methadone pharmacokinetics in children and adults with SCD, with a secondary aim to assess pain relief and opioid consumption.
  
  
  
  Participants included children (<18 years) and adults with a VOE requiring hospitalization. Patients were randomly assigned to receive standard care (opioid patient-controlled analgesia; control group) or one dose of intravenous methadone (0.1-0.125 mg/kg) in addition to standard care (methadone group). Venous methadone and metabolite concentrations were measured. Pain scores, pain relief scores, and opioid consumption were recorded.
  
  
  
  Twenty-four children (12 methadone, 12 controls) and 23 adults (11 methadone, 12 controls) were studied. In children, the half-life of R- and S-methadone enantiomers was 34 ± 16 and 24 ± 9 hr, respectively. In adults, R- and S-methadone half-lives were 52 ± 17 and 38 ± 12 hr, respectively. Pain scores were lower (P = 0.002) and pain relief scores were higher (P = 0.0396) in children receiving methadone versus controls. There was no difference in pain scores and pain relief in adults receiving methadone versus controls. There was no difference in opioid consumption between methadone and control groups, in both adults and children.
  
  
  
  Intravenous methadone disposition in children and adults with SCD was comparable to that in subjects without SCD from prior studies. Methadone produced more pain relief than standard care in children with SCD. Higher methadone doses may be more effective and should be evaluated in both children and adults with SCD.
authors: Department of Pediatrics, Washington University in St Louis, St Louis, Missouri.
authors: Jennifer
authors: J
authors: Horst
authors: Department of Pediatrics, Washington University in St Louis, St Louis, Missouri.
authors: Melissa
authors: M
authors: Frei-Jones
authors: Department of Internal Medicine, Washington University in St Louis, St Louis, Missouri.
authors: Elena
authors: E
authors: Deych
authors: Department of Internal Medicine, Washington University in St Louis, St Louis, Missouri.
authors: William
authors: W
authors: Shannon
authors: Department of Anesthesiology, Washington University in St Louis, St Louis, Missouri. kharasch@wustl.edu.|Department of Biochemistry and Biophysics, Washington University in St Louis, St Louis, Missouri. kharasch@wustl.edu.|The Center for Clinical Pharmacology, St Louis College of Pharmacy and Washington University School of Medicine, St Louis, Missouri. kharasch@wustl.edu.
authors: Evan D
authors: ED
authors: Kharasch
mesh_terms: D000293:Adolescent; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000493:pharmacokinetics* / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone
keywords: analgesics; methadone; pediatric; sickle cell disease