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Single‐Dose Pharmacokinetic Study of Tramadol Extended‐Release Tablets in Children and Adolescents
Author(s) -
Vandenbossche Joris,
Peer Achiel,
Richards Henry
Publication year - 2016
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.266
Subject(s) - tramadol , medicine , pharmacokinetics , adverse effect , nausea , area under the curve , dosing , anesthesia , vomiting , cyp2d6 , gastroenterology , analgesic , cytochrome p450 , metabolism
Combined analyses from 2 open‐label, phase‐1 studies—the pharmacokinetic profile of tramadol and its metabolite (M1) following a single oral dose of tramadol extended release (ER) (25 to 100 mg) in children (7 to 11 years old; study 1: n = 37) and adolescents (12 to 17 years old; study 2: n = 38) with painful conditions—were historically compared with that of healthy adults following similar dosing. The dose‐normalized area under the curve (DN AUC 0‐24h ) and maximum concentration (DN C max ) of tramadol and of M1 in children and in adolescents were lower than those in adults (children vs adults: tramadol, DN AUC 0‐24h 82.19%; DN C max 80.38%, P = .0031; M1, DN AUC 0‐24h 51.19% , DN C max 52.68%, P < .0001; adolescents vs adults: tramadol, DN AUC 0‐24h 89.56%, DN C max 84.01%; M1, DN AUC 0‐24h 85.28%, DN C max 83.03%, P = .0004). The arithmetic mean terminal elimination t 1/2 of tramadol in children and adolescents was comparable to that in adults (children 8.4 hours; adolescents 8.5 hours; adults 7.9 hours). The most frequently reported (≥5% of participants) treatment‐emergent adverse events in children included headache, upper abdominal pain and constipation, and in adolescents were headache, nausea, dizziness, and stomach discomfort. Multiple factors may have contributed to these observations, including a higher proportion of children (56%) who may have a lower activity of CYP2D6, resulting in reduced clearance of tramadol.