title: Pharmacokinetics of tramadol after subcutaneous administration in a critically ill population and in a healthy cohort.
abstract: BACKGROUND
  Tramadol is an atypical centrally acting analgesic agent available as both oral and parenteral preparations. For patients who are unable to take tramadol orally, the subcutaneous route of administration offers an easy alternative to intravenous or intramuscular routes. This study aimed to characterise the absorption pharmacokinetics of a single subcutaneous dose of tramadol in severely ill patients and in healthy subjects.
  
  
  METHODS
  Blood samples (5 ml) taken at intervals from 2 minutes to 24 hours after a subcutaneous dose of tramadol (50 mg) in 15 patients (13 male, two female) and eight healthy male subjects were assayed using high performance liquid chromatography. Pharmacokinetic parameters were derived using a non-compartmental approach.
  
  
  RESULTS
  There were no statistically significant differences between the two groups in the following parameters (mean ± SD): maximum venous concentration 0.44 ± 0.18 (patients) vs. 0.47 ± 0.13 (healthy volunteers) mcg/ml (p = 0.67); area under the plasma concentration-time curve 177 ± 109 (patients) vs. 175 ± 75 (healthy volunteers) mcg/ml*min (p = 0.96); time to maximum venous concentration 23.3 ± 2 (patients) vs. 20.6 ± 18.8 (healthy volunteers) minutes (p = 0.73) and mean residence time 463 ± 233 (patients) vs. 466 ± 224 (healthy volunteers) minutes (p = 0.97).
  
  
  CONCLUSIONS
  The similar time to maximum venous concentration and mean residence time suggest similar absorption rates between the two groups. These results indicate that the same dosing regimens for subcutaneous tramadol administration may therefore be used in both healthy subjects and severely ill patients.
  
  
  BACKGROUND
  ACTRN12611001018909.
authors.affiliation: Department of Anaesthesia, Pain Medicine and Hyperbaric Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Dooney
authors.affiliation: Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia ; Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Krishnaswamy
authors.initials: K
authors.lastname: Sundararajan
authors.affiliation: Department of Anaesthesia, Pain Medicine and Hyperbaric Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia.
authors.forename: Tharapriya
authors.initials: T
authors.lastname: Ramkumar
authors.affiliation: Discipline of Pharmacology, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Somogyi
authors.affiliation: Department of Anaesthesia, Pain Medicine and Hyperbaric Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia ; Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia ; Discipline of Pharmacometrics, Division of Health Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Upton
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ong
authors.affiliation: Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia ; Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: O'Connor
authors.affiliation: Intensive Care Unit, Royal Adelaide Hospital, Adelaide, Australia ; Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: Department of Anaesthesia, Pain Medicine and Hyperbaric Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia ; Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Guy L
authors.initials: GL
authors.lastname: Ludbrook
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016638:Critical Illness; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D014147:Tramadol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol
keywords: Healthy subjects; Pharmacokinetics; Severely ill; Subcutaneous; Tramadol