There is extensive between-subject variation in the pharmacokinetics (PK) of oxycodone in preterm neonates and newborns, and their hepatic clearance (CL) is low and volume of distribution large. In elderly individuals, oxycodone CL is slightly lower and volume of distribution is slightly smaller compared with young adults. |
In pregnant or labouring women, oxycodone passes freely through the placenta; oxycodone concentrations are similar in maternal and fetal plasma. Low concentrations of oxycodone are found in mothers’ milk. |
Interactions with cytochrome P450 (CYP) 3A inhibitors and inducers with/without CYP2D6 inhibitors can substantially affect the PK and pharmacodynamics (PD) of oxycodone. These interactions must be taken into account in patients using, starting, or discontinuing CYP3A inducer(s) or inhibitor(s) with/without CYP2D6 inhibitor(s) during oxycodone treatment. |
Transmucosal administration is a feasible option in acute pain management for those patients with no intravenous line in place, while epidural administration is an option in those patients with an epidural catheter in place. However, further data are needed on the safety and efficacy of intrathecal oxycodone. |
1 Introduction
2 Basic Pharmacokinetics (PK)
Parameter | Intravenously, 0.07 mg/kg [10] | Intramuscularly, 0.14 mg/kg [11] | Orally, liquid, 0.28 mg/kg [11] | Orally, IR tablet, 5 mg [166] | Orally, CR tablet, 10 mg [166] |
---|---|---|---|---|---|
Vss (L/kg) | 2.6 [1.8–3.7] | ||||
CL (L/min) | 0.82 [0.4–1.3] | 0.78 (0.2) | |||
Cmax (ng/mL) | 34 (10) | 38 (14) | 15.6 (4.4) | 15.1 (4.7) | |
Tmax (h) | 1.0 [0.5–1.5] | 1.0 [0.5–1.0] | 1.4 (0.7) | 3.2 (2.2) | |
t½el (h) | 3.0 [1.8–9.7] | 4.9 (0.8) | 5.1 (1.7) | ||
AUC (ng/mL/h) | 208 (49) | 245 (84) | 99 (36) | 104 (40) | |
Bioavailability | 0.6 (0.2) | ||||
NOR:OXY ratio | 0.3 [0.06–0.83] | 0.45 (0.23) | 0.64 (0.24) |
3 Cytochrome P450 2D6 Polymorphism and Oxycodone
4 Central Nervous System Penetration
5 Oxycodone in Renal and Hepatic Insufficiency
6 Sex Differences in the PK of Oxycodone
7 Oxycodone During Pregnancy and Lactation
8 Oxycodone in Children
9 Oxycodone in the Elderly
10 Oxycodone in Patients Undergoing Laparoscopic versus Open Surgery
Settings | Concomitant analgesics | MEC (ng/mL) | MEAC (ng/mL) | Note | References |
---|---|---|---|---|---|
Open heart surgery | Fentanyl infusion stopped 10–12 h earlier | 5–6 | P-fentanyl 1.4 ng/mL | [167] | |
Laparoscopic cholecystectomy | – | 21–34 | 47–55 | [96] | |
Laparoscopic cholecystectomy | Intravenous acetaminophen 1/2 g | 25/24 | 70/62 | [168] | |
Laparoscopic cholecystectomy | Intravenous dexketoprofen 10/50 mg | 60/52 | 98/80 | [169] | |
Laparotomy | – | 32–63 | 74–76 | [170] | |
Midline laparotomy | Acetaminophen + rectus sheath block | 18–27 | At 24 h after surgery | [171] | |
Breast cancer surgery | Fentanyl 1 µg/kg | 22 | 33 | Extensive surgery: MEC 31, MEAC 51 | [103] |
11 Cancer Pain and Cachexic Patients
12 Oxycodone in Neuropathic Pain
13 Oxycodone in Neuraxial Anaesthesia
14 Transmucosal Oxycodone
15 Abuse-Deterrent Formulations
16 Drug Interactions
Concomitant compound | Contributing enzyme | Effect on the pharmacokinetics and pharmacodynamics of oxycodone | References |
---|---|---|---|
Telithromycin 800 mg for 4 days | CYP3A4 inhibitor | Oxycodone: AUC ↑ 78%; noroxycodone: AUC ↓ 47%. Drug effect ↑, performance ↓, pupil ↓ | [151] |
Voriconazole 400–600 mg for 4 days | CYP3A4 inhibitor | Oxycodone: AUC ↑ 261%, Cmax ↑ 72%; oxymorphone: AUC ↑ 627%, Cmax ↑ 108%; noroxycodone: AUC ↓ 170%, Cmax ↓ 100–170%: noroxymorphone: AUC ↓ 53%, Cmax ↓ 89%. Drug effect ↑, pupil ↓, pain thresholds ↑, pain ↓ | [155] |
Ketoconazole 400 mg 2 h before/200 mg 48, 24 and 2 h before | CYP3A4 inhibitor | Oxycodone: AUC ↑ 83–145%, Cmax ↔/↑ 77%; oxymorphone AUC ↑ 246%, Cmax ↑ 14–43%; noroxycodone AUC ↓ 14%, Cmax ↑ −45–127%; noroxymorphone: AUC ↓ 43%, Cmax ↓ 85%. Drug effect ↔, psychomotor performance ↓, pain ↓, pupil ↓ | |
Clarithromycin 500 mg for 5 days | CYP3A4 inhibitor | Oxycodone: AUC ↑ 102–131%, Cmax ↑ 45–68%; oxymorphone: AUC ↑ 208–264%, Cmax ↑ 32–72%; noroxycodone: AUC ↓ 46–47%, Cmax ↓ 59–67%; noroxymorphone: AUC ↓ 40–62%, Cmax ↓ 57–71%. Drug effect ↔, pupil ↔, pain ↔ | [150] |
Rifampin 600 mg for 7 days | CYP3A4 inducer | Oxycodone: AUC ↓ 53–86%, Cmax ↓ 63%; oxymorphone: AUC ↓ 90–95%, Cmax ↓ 62%; noroxycodone: AUC ↔, Cmax ↑ 87%; noroxymorphone: AUC ↑ 23%, Cmax ↑ 121%. Drug effect ↔, pupil ↔ | [12] |
Quinidine 300 mg 6 h before and 100 mg 3 h after/100 mg 2 h before | CYP2D6 inhibitor | Oxycodone: AUC ↑ 13–46%, Cmax ↔; oxymorphone: AUC ↓ 10%, Cmax ↓ 42%; noroxycodone AUC ↑ 72%, Cmax ↑ 20%; noroxymorphone: AUC ↓ 81%, Cmax ↓ 79%. Drug effect ↔/↓, psychomotor performance ↔/↓, pain ↔, pupil ↔ | |
Paroxetine 20 mg for 5–7 days/20 mg 48, 24 and 2 h before | CYP2D6 inhibitor | Oxycodone: AUC ↑ 11–12%/↔, Cmax ↔; oxymorphone: AUC ↓ 44–66%, Cmax ↓ 33–47%; noroxycodone: AUC ↑ 68–70%, Cmax ↑ 30–37%/↔; noroxymorphone: AUC ↓ 74–95%, Cmax ↓ 75–80%. Drug effect ↔/↑, pupil ↑, pain ↔/↑ | |
Paroxetine 20 mg and itraconazole 200 mg for 5 days | CYP2D6 and CYP3A4 inhibitor | Oxycodone: AUC ↑ 97–188%, Cmax ↑ 77%; oxymorphone: AUC ↔ − 38%/+ 22%, Cmax ↓ 15–32%; noroxycodone: AUC ↓ 12–15%, Cmax ↓ 46–61%; noroxymorphone: AUC ↓↓↓, Cmax ↓↓↓. Drug effect ↔/↑, pupil ↑, pain ↔ | |
Quinidine 100 mg and ketoconazole 400 mg 2 h before | CYP2D6 and CYP3A4 inhibitor | Oxycodone: AUC ↑ 209%, Cmax ↑ 58%; oxymorphone: AUC ↑ 59%, Cmax ↑ 43%; noroxycodone: AUC ↑ 178%, Cmax ↑ 260%; noroxymorphone: AUC ↓↓↓, Cmax ↓↓. Drug effect ↑, psychomotor performance ↓, pain ↓, pupil ↓ | [18] |
Miconazole oral gel 255 mg for 4 days | CYP2D6 and CYP3A4 inhibitor | Oxycodone AUC ↑ 63%, Cmax ↑ 31%; oxymorphone AUC ↓ 83%, Cmax ↓ 64%; noroxycodone: AUC ↑ 30%, Cmax ↓ 20%; noroxymorphone: AUC ↓ 76%, Cmax ↓ 73%. Drug effect ↑, pupil ↔ | [154] |
Lopinavir/ritonavir 400 mg/100 mg for 4 days | CYP3A, CYP2D6, and P-gp inhibitor | Oxycodone AUC ↑ 157%, Cmax ↑ 38%; oxymorphone AUC ↑ 169%; noroxycodone: AUC ↓ 64%; noroxymorphone: AUC ↓ 76%. Drug effect ↑ | [156] |
Ritonavir 600 mg for 4 days | CYP3A, CYP2D6 and P-gp inhibitor | Oxycodone: AUC ↑ 195%, Cmax ↑ 74%; oxymorphone: AUC ↓ 28%; noroxycodone: AUC ↓ 51%; noroxymorphone: AUC ↓ 81%. Drug effect ↑ | [156] |
Grapefruit juice 600 ml for 5 days | CYP3A and P-gp (?) inhibitor | Oxycodone: AUC ↑ 62%, Cmax ↑ 42%; oxymorphone: AUC ↑ 44%, Cmax ↑ 22%; noroxycodone: AUC ↔, Cmax ↓ 24%; noroxymorphone: AUC ↓ 43%, Cmax ↓ 27%. Drug effect ↑, pain ↔ | [172] |
Itraconazole 200 mg for 5 days | CYP3A and P-gp (?) inhibitor | Oxycodone: AUC ↑ 51–144%, Cmax ↑ 45%; oxymorphone: AUC ↑ 159–359%, Cmax ↑ 11–48%; noroxycodone: AUC ↓ 49%, Cmax ↓ 71%; noroxymorphone: AUC ↓ 71–84%, Cmax ↓ 73–85%. Drug effect ↑, pain ↔ | [152] |
St John’s wort 900 mg for 15 days | CYP3A4 inducer | Oxycodone: AUC ↓ 50%, Cmax ↓ 28%; oxymorphone: AUC ↓ 52%, Cmax ↓ 22%; noroxycodone: AUC ↑ 13%, Cmax ↑ 51%; noroxymorphone: AUC ↑ 22%, Cmax ↑ 73%. Drug effect ↓, pain threshold ↓ | [157] |