Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease

Abstract

Background Vaso-occlusive episodes (VOE) 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. Procedure Participants included children (<18 yr) 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. Results Twenty-four children (12 methadone, 12 controls) and twenty-three 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. Pain scores were lower (p=0.002) and pain relief scores were higher (p=0.0396) in children receiving methadone vs controls. There was no difference in pain scores and pain relief in adults receiving methadone vs controls. There was no difference in opioid consumption between methadone and control groups, in both adults and children. Conclusions Intravenous methadone disposition in children and adults with SCD was comparable to 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.

Inhibitory effect of isavuconazole, ketoconazole, and voriconazole on the pharmacokinetics of methadone in vivo and in vitro

“…Methadone taken orally is subjected to an important first‐pass effect and is detectable in the plasma about 30 minutes after administration . Its bioavailability varies from 41–76% to 85–95% .…”

“…25 Methadone taken orally is subjected to an important first-pass effect and is detectable in the plasma about 30 minutes after administration. 26,27 Its bioavailability varies from 41-76% to 85-95%. 28,29 In our study, co-administration with isavuconazole, ketoconazole and voriconazole, the main pharmacokinetic parameters of methadone changed more or less.…”

Methadone for Analgesia in Children with Life-Limiting Illness: Experience from a Tertiary Children’s Health Service

“…Routes of administration can include oral, rectal, nasal, sublingual, subcutaneous, epidural or intravenous [ 6 ]. The half-life of methadone varies significantly between individuals and over time, and is shorter in children, [ 7 , 8 , 9 ]. With chronic administration the half-life in adults drops from 54.8 h to 24 h [ 10 ].…”

Management of severe chronic pain with methadone in pediatric patients with sickle cell disease

“…The study did not identify a difference in pain response between short and long acting opioids but was not focused on the impact of methadone on decreasing healthcare utilization among patients with SCD experiencing chronic pain . For acute pain benefit, a single dose of intravenous (IV) methadone was recently shown to have improved pain scores when used in addition to standard of care pain relief strategies in hospitalized children and adult patients with SCD …”

“…6 For acute pain benefit, a single dose of intravenous (IV) methadone was recently shown to have improved pain scores when used in addition to standard of care pain relief strategies in hospitalized children and adult patients with SCD. 7 There are concerns for methadone use worth noting, including prolongation of the QTc interval. A Finnish toxicity study identified patients treated with methadone having the highest fatal toxicity index.…”