title: Pharmacokinetics of oxycodone after subcutaneous administration in a critically ill population compared with a healthy cohort.
abstract: This study aimed to characterise and compare the absorption pharmacokinetics of a single subcutaneous dose of oxycodone in critically ill patients and healthy subjects. Blood samples taken at intervals from two minutes to eight hours after a subcutaneous dose of oxycodone in patients (5 mg) and healthy volunteers (10 mg) were assayed using high performance liquid chromatography. Data were analysed using a non-compartmental approach and presented as mean (SD). Parameters were corrected for dose differences between the groups assuming linear kinetics. Ten patients (eight male, two female) and seven healthy male subjects were included. Maximum venous concentration and area under the concentration curve were approximately two-fold lower in the patient group for an equivalent dose, suggesting either reduced bioavailability or increased clearance: maximum venous concentration 0.14 ± 0.06 vs 0.05 ± 0.02 µg/ml (P <0.0001); area under the concentration curve 19.50 ± 9.15 vs 9.72 ± 2.71 µg/ml/minute (P <0.001) respectively. However, time to maximum venous concentration and mean residence time were not different, suggesting similar absorption rates: time to maximum venous concentration 22.10 ± 18.0 vs 20.50 ± 16.10 minutes (P=0.81); mean residence time 353 ± 191 vs 291 ± 80 minutes (P=0.26). Kinetic parameters were less variable in patients than in volunteers. The patients therefore had reduced exposure to subcutaneous oxycodone. This warrants further model-based analysis and experimentation. Dose regimens for subcutaneous oxycodone developed in healthy volunteers cannot be directly translated to critically ill patients.
authors.affiliation: Department of Intensive Care, Royal Adelaide Hospital, Adelaide, South Australia, Australia. ravibk123@gmail.com
authors.forename: R B
authors.initials: RB
authors.lastname: Krishnamurthy
authors.forename: R N
authors.initials: RN
authors.lastname: Upton
authors.forename: A O
authors.initials: AO
authors.lastname: Fajumi
authors.forename: S
authors.initials: S
authors.lastname: Lai
authors.forename: C S
authors.initials: CS
authors.lastname: Charlton
authors.forename: R M
authors.initials: RM
authors.lastname: Ousley
authors.forename: A M
authors.initials: AM
authors.lastname: Martinez
authors.forename: H
authors.initials: H
authors.lastname: McConnell
authors.forename: S N
authors.initials: SN
authors.lastname: O'Connor
authors.forename: J
authors.initials: J
authors.lastname: Ong
authors.forename: P E
authors.initials: PE
authors.lastname: Macintyre
authors.forename: M J
authors.initials: MJ
authors.lastname: Chapman
authors.forename: G L
authors.initials: GL
authors.lastname: Ludbrook
mesh_terms: D000042:Absorption; D000328:Adult; D000368:Aged; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D016638:Critical Illness; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010098:Oxycodone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010146:Pain / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D010098:Oxycodone; D005283:Fentanyl