Central nervous system penetration of oxycodone after intravenous and epidural administration

Kokki, Merja; Välitalo, Pyry A. J.; Kuusisto, M.; Ranta, Veli‐Pekka; Raatikainen, Kaisa; Hautajärvi, Heidi; Kokki, Hannu

doi:10.1093/bja/aet337

Cited by 52 publications

(94 citation statements)

References 21 publications

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“…In the present study, CSF oxycodone levels in the EPI group were approximately 100‐fold higher than in the IV group. However, the observed peak concentrations in the present study were approximately one‐quarter of those in our previous study . The most likely explanation for this is that, in the present study, CSF samples were collected at the L4–5 level by a single puncture, whereas in the previous study a spinal catheter was used for CSF sampling, with the tip higher in the subarachnoid space.…”

Section: Discussionmentioning

confidence: 99%

“…Epidural administration of oxycodone has been evaluated in few previous clinical trials . In the study by Bäcklund et al .…”

Section: Discussionmentioning

confidence: 99%

“…Respiratory depression and neurotoxicity are the main concerns with any compounds injected epidurally. In both our previous pharmacokinetic study and the present study, no signs or symptoms of neural irritation were noted. An in vitro study that we conducted in human neuroblastoma and mouse motoneuronal cell cultures suggested that the neuronal toxicity of oxycodone is similar to or less than that of morphine .…”

Section: Discussionmentioning

confidence: 99%

“…fentanyl with i.v. oxycodone was 0.36 (0.08) mg during the first 4 h after gynaecological laparotomy . In order to show a decrease of 50% (i.e.…”

Section: Methodsmentioning

confidence: 99%

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The analgesic efficacy and pharmacokinetics of epidural oxycodone after gynaecological laparotomy: a randomized, double‐blind, double‐dummy comparison with intravenous administration

Piirainen

Kokki

Hautajärvi

et al. 2018

Brit J Clinical Pharma

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Section: Discussionmentioning

confidence: 99%

“…Epidural administration of oxycodone has been evaluated in few previous clinical trials . In the study by Bäcklund et al .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…fentanyl with i.v. oxycodone was 0.36 (0.08) mg during the first 4 h after gynaecological laparotomy . In order to show a decrease of 50% (i.e.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

The analgesic efficacy and pharmacokinetics of epidural oxycodone after gynaecological laparotomy: a randomized, double‐blind, double‐dummy comparison with intravenous administration

Piirainen

Kokki

Hautajärvi

et al. 2018

Brit J Clinical Pharma

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“…Animal experiments also showed that the κ receptor [7,8,9] is related to the relief of visceral pain. Therefore, the control of oxycodone on postoperative recovery period of acute pain in visceral pain may be better after laparoscopic resection of rectal tumor [10,11] . 2.…”

Section: Discussionmentioning

confidence: 99%

A Single Intravenous Injection of Oxycodone Hydrochloride In The Treatment of Acute Post-operative Pain after Laparoscopic Rectal Tumor Resection

et al. 2017

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Abstract. Objective: To investigate the efficacy of a single intravenous injection of oxycodone hydrochloride in patients undergoing laparoscopic rectal tumor resection with acute postoperative pain and evaluate the quality of Anesthesia recovery period. Methods:60 patients for laparoscopic rectal tumor resection, were randomly divided into two groups (n=30 each): oxycodone hydrochloride injection group (group I) and fentanil injection group (group II). oxycodone 0.05mg / kg (saline dilution of 1mg / ml) or fentanil 0.1ug / kg was injected intravenously at the end of surgery. Assessing the OAA / S sedation grade and Prince-Henry postoperative pain scores. Results Demographic data and anesthesia characteristics were similar in the two groups. Group II's Prince-Henry pain score was significantly higher than the group I's (P <0.01). Conclusion: xycodone injection can reduce the incidence of acute pain after Laparoscopic rectal tumor resection, and effectively relieve the occurred acute pain, the clinical use of oxcodone is safe and effective. BackgroundAt present, the proportion of laparoscopic surgery in the surgical operation increased year by year because of its small trauma and fast recovery. The pain after laparoscopic operation has aroused great attention. The pain of visceral and radiation were more obvious after laparoscopic surgery in addition to the pain of operative incision by stretching stimulation of the diaphragmatic peritoneum and artificial carbon dioxide pneumoperitoneum and position and so on. Most clinical use of analgesics is opioid now [1] . However, it is limiting use in the recovery period because of the respiratory depression and other side effects of opioid analgesics. Oxycodone, a potent semi synthetic opioid drugs,is a type of double receptor agonist of opioid (μ receptor and κ receptor), and is widely used in moderating to severe cancer pain, postoperative acute pain and neuropathic pain [2] . The pharmacological effects of oxycodone is similar with morphine [3] . The analgesic effect of visceral pain of oxycodone is better than other opioid drug. The prominent advantage is that the sedation and respiratory depression a Corresponding

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Physiologically based pharmacokinetic modelling of oxycodone drug–drug interactions

Rytkönen

Ranta

Kokki

et al. 2020

Biopharm & Drug Disp

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Oxycodone is an opioid analgesic with several pharmacologically active metabolites and relatively narrow therapeutic index. Cytochrome P450 (CYP) 3A4 and CYP2D6 play major roles in the metabolism of oxycodone and its metabolites. Thus, inhibition and induction of these enzymes may result in substantial changes in the exposure of both oxycodone and its metabolites. In this study, a physiologically based pharmacokinetic (PBPK) model was built using GastroPlus™ software for oxycodone, two primary metabolites (noroxycodone, oxymorphone) and one secondary metabolite (noroxymorphone). The model was built based on literature and in house in vitro and in silico data. The model was refined and verified against literature clinical data after oxycodone administration in the absence of drug-drug interactions (DDI). The model was further challenged with simulations of oxycodone DDI with CYP3A4 inhibitors ketoconazole and itraconazole, CYP3A4 inducer rifampicin and CYP2D6 inhibitor quinidine. The magnitude of DDI (AUC ratio) was predicted within 1.5-fold error for oxycodone, within 1.8-fold and 1.3-4.5-fold error for the primary metabolites noroxycodone and oxymorphone, respectively, and within 1.4-4.5-fold error for the secondary metabolite noroxymorphone, when compared to the mean observed AUC ratios. This work demonstrated the capability of PBPK model to simulate DDI of the administered compounds and the formed metabolites of both DDI victim and perpetrator. However, the predictions for the formed metabolites tend to be associated with higher uncertainty than the predictions for the administered compound. The oxycodone model provides a tool for forecasting oxycodone DDI with other CYP3A4 and CYP2D6 DDI perpetrators that may be coadministered with oxycodone.

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Central nervous system penetration of oxycodone after intravenous and epidural administration

Abstract: EudraCT reference number: 2011-000125-76.

Cited by 52 publications

References 21 publications

The analgesic efficacy and pharmacokinetics of epidural oxycodone after gynaecological laparotomy: a randomized, double‐blind, double‐dummy comparison with intravenous administration

The analgesic efficacy and pharmacokinetics of epidural oxycodone after gynaecological laparotomy: a randomized, double‐blind, double‐dummy comparison with intravenous administration

A Single Intravenous Injection of Oxycodone Hydrochloride In The Treatment of Acute Post-operative Pain after Laparoscopic Rectal Tumor Resection

Physiologically based pharmacokinetic modelling of oxycodone drug–drug interactions

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