title: Pharmacokinetics of hydrocodone/acetaminophen combination product in children ages 6-17 with moderate to moderately severe postoperative pain.
abstract: Lortab® Elixir, a proprietary combination product containing hydrocodone and acetaminophen, is approved in the US for the treatment of moderate to moderately severe pain in children. Despite this approval, pediatric pharmacokinetic data using this product have not been previously published. Using a single-dose open-label study approach, we evaluated the pharmacokinetics, tolerability, and safety of this product in 17 healthy children 6-17 years of age. Results showed that the body weight-normalized oral clearance (L/h/kg) of hydrocodone and acetaminophen were 42% and 27% higher, respectively when compared to data from healthy adults. This suggests that a higher mg/kg dose would be required in children to achieve exposures similar to adults. We found adjustment of hydrocodone and acetaminophen dose by body surface area to be more optimal than body weight-based dose adjustments for achieving similar systemic exposure in children and adults. However, body weight-based hydrocodone and acetaminophen dosing regimens provided close approximation of adult exposures in pediatric patients with approximately 22% to 24% lower hydrocodone and acetaminophen dose/BW-normalized AUC in pediatric patients compared to adults. Finally, the adverse event profile in our pediatric cohort was consistent with that expected of opioid-naive subjects receiving opioid-combination therapy.
authors.affiliation: Department of Clinical Pharmacology and Pharmacometrics, R&D, AbbVie Inc, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dutta
authors.forename: Greg
authors.initials: G
authors.lastname: Kearns
authors.forename: Walid
authors.initials: W
authors.lastname: Awni
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Neville
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000293:Adolescent; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001830:Body Surface Area; D001835:Body Weight; D002648:Child; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D010149:Postoperative Pain / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D004338:Drug Combinations; C083640:acetaminophen, hydrocodone drug combination; D000082:Acetaminophen; D006853:Hydrocodone
keywords: Lortab; acetaminophen; hydrocodone; opioid; pediatric; pharmacokinetics