Perioperative Pharmacokinetics of Methadone in Adolescents

Abstract

Background Methadone is frequently used in adult anesthesia and pain treatment. Methadone pharmacokinetics in adults are well characterized, including the perioperative period. Methadone is also used in children. There is, however, no information on methadone pharmacokinetics in children of any age. The purpose of this investigation was to determine the pharmacokinetics of intravenous methadone in children undergoing surgery. Perioperative opioid-sparing effects were also assessed. Methods Eligible subjects were children 5–18 yr undergoing general anesthesia and surgery, with an anticipated postoperative inpatient stay exceeding 3d. Three groups of 10–11 patients each received intravenous methadone HCl after anesthetic induction in ascending dose groups of 0.1, 0.2, and 0.3 mg/kg (up to 20 mg). Anesthetic care was not otherwise changed. Venous blood was obtained for 4d, for stereoselective determination of methadone and metabolites. Pain assessments were made each morning. Daily and total opioid consumption was determined. Perioperative opioid consumption and pain was determined in a second cohort, which was matched to age, sex, race, ethnicity, surgical procedure, and length of stay, but not receiving methadone. Results The final methadone study cohort was 31 adolescents (14 ± 2 yr, range 10–18) undergoing major spine surgery for a diagnosis of scoliosis. Methadone pharmacokinetics were linear over the dose range 0.1–0.3 mg/kg. Disposition was stereoselective. Methadone administration did not dose-dependently affect postoperative pain scores, and did not dose-dependently decrease daily or total postoperative opioid consumption in spinal fusion patients. Conclusions Methadone enantiomers disposition in adolescents undergoing surgery was similar to that in healthy adults.

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

“…Plasma was obtained by centrifugation and stored at –80°C until analysis. Plasma concentrations of methadone and the primary (inactive) metabolite EDDP were determined by liquid chromatography–tandem mass spectrometry as previously described …”

The Hematological Effects of Nitrous Oxide Anesthesia in Pediatric Patients

“…8 Washington University in St. Louis’ IRB approved both the parent study and our retrospective analysis. All participants and their parents/legal guardians provided written assent/consent for the original study, and a waiver of consent was approved for this retrospective analysis.…”

“…The sample size basis of the parent studies 2,8 is not related to this study. Subjects were categorized into 3 groups based on nitrous oxide use: patients who received nitrous oxide for the entire duration of anesthesia (maintenance group), patients who received nitrous oxide only during induction and/or emergence (induction/emergence group), and patients who did not receive nitrous oxide (nitrous oxide-free group).…”

MethadoneN-Demethylation by the CommonCYP2B6Allelic Variant CYP2B6.6

“…Reactions (10-minute) were quenched with 20 ml 20% trichloroacetic acid containing internal standard (d3-EDDP, final concentration 4.55 ng/ml) and centrifuged; the supernatant (200 ml) was processed immediately by solid-phase extraction as described previously (Kharasch et al, 2004), except that Strata-X-C 33 mm plates (Phenomenex, Torrance, CA) were used. EDDP analysis was performed on an API 3200 triple-quadrupole mass spectrometer with Turbo Ion Spray source (Applied Biosystems/MDS Sciex, Foster City, CA), Shimadzu high-pressure liquid chromatographer (Columbia, MD), Gerstel autosampler (Baltimore, MD), and Chrom Tech chiral AGP column (3 Â 50 mm, 5 mm) with chiral AGP guard cartridge (3 Â 10 mm) (Apple Valley, MN), as described (Sharma et al, 2011), except that the mobile phase gradient was 20 mM ammonium formate (pH 5.0) and methanol. Retention times were 10.4 and 11.2 minutes, respectively, for Rand S-EDDP.…”