Single- and multiple-dose pharmacokinetic studies of tramadol immediate-release tablets in children and adolescents

Clin Pharmacol Drug Dev. 2015 May-Jun;4(3):184-92. doi: 10.1002/cpdd.169. Epub 2014 Dec 22.

Abstract

In these combined analyzes from 3 open-label, phase-1 studies, the pharmacokinetic profile of tramadol and its metabolite (M1) following administration of tramadol immediate-release (IR) tablets in children and adolescents, 7-16 years old (studies 1 and 2: n = 38; study 3: n = 21) with painful conditions following single oral dose of tramadol IR (25-100 mg) (studies 1 and 2) or multiple oral doses of tramadol IR tablets every 6 hours for 3 days (study 3) were compared with that of healthy adults following similar treatment. Area under the curve of tramadol and its metabolite M1 in children and adolescents was lower compared with adults (Dose-normalized [DN] AUC, h ng/mL: tramadol: 1316.87 [children]; 1418.02 [adolescents];1838.29 [adults]; M1: 342.56 [children]; 475.4 [adolescents]; 636.13 [adults]) while the Cmax remained similar (DN Cmax , ng/mL: tramadol: 203.75 [children]; 165.35 [adolescents]; 226.92 [adults]; M1: 34.93 [children]; 38.42 [adolescents]; 52.14 [adults]). The DN AUC was further lower in children and adolescents with a lower body weight (<50 kg). The weight normalized oral clearance of tramadol was higher in children and adolescents compared with adults (CL/F, mL/min/kg: 12.66 [children]; 11.75 [adolescents]; 9.06 [adults]). No new safety findings emerged. Tramadol was generally safe and well-tolerated by children and adolescents with painful conditions.

Keywords: adolescents; pain; pediatric; pharmacokinetics; tramadol-immediate release.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Age Factors
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / pharmacokinetics*
  • Area Under Curve
  • Biotransformation
  • Child
  • Drug Administration Schedule
  • Drug Compounding
  • Female
  • Humans
  • Male
  • Models, Biological
  • Pain / blood
  • Pain / diagnosis
  • Pain / drug therapy*
  • Pain Measurement
  • Tramadol / administration & dosage*
  • Tramadol / adverse effects
  • Tramadol / pharmacokinetics*
  • Treatment Outcome
  • United States

Substances

  • Analgesics, Opioid
  • Tramadol