Kinnunen, M, Kokki, H, Hautajärvi, H, et al. Oxycodone concentrations in the central nervous system and cerebrospinal fluid after epidural administration to the pregnant ewe. Basic Clin Pharmacol Toxicol. 2019; 125: 430– 438. https://doi.org/10.1111/bcpt.13276
Oxycodone concentrations in the central nervous system and cerebrospinal fluid after epidural administration to the pregnant ewe
|Author:||Kinnunen, Mari1; Kokki, Hannu1; Hautajärvi, Heidi2;|
1School of Medicine, University of Eastern Finland, Kuopio, Finland
2Admescope Ltd, Oulu, Finland
3Department of Obstetrics and Gynaecology, Oulu University Hospital and University of Oulu, Oulu, Finland
4Department of Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
5Laboratory Animal Centre, Department of Experimental Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland
6Department of Anaesthesia and Intensive Care, Kuopio University Hospital, Kuopio, Finland
|Online Access:||PDF Full Text (PDF, 0.6 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019111943062
John Wiley & Sons,
|Publish Date:|| 2020-06-21
The main sites of the analgesic action of oxycodone are the brain and spinal cord. The present study describes the concentrations of oxycodone and its metabolites in the brain and spinal cord after epidural administration to the ewe. Twenty pregnant ewes undergoing laparotomy were randomized into two groups to receive epidural oxycodone: infusion group (n = 10, 0.1 mg·kg−1 bolus followed by continuous infusion of 0.05 mg·kg−1·h−1 for five days) or repeated boluses group (n = 10, 0.2 + 2x0.1 mg·kg−1 bolus followed by a 0.2 mg·kg−1 bolus every 12 hours for five days). After five days of oxycodone administration, arterial blood samples were collected, the sheep were killed, and a CSF sample and tissue samples from the cortex, thalamus, cerebellum and spinal cord were obtained for the quantification of oxycodone and its main metabolites. The median plasma and CSF concentrations of oxycodone were 9.0 and 14.2 ng·mL−1 after infusion and 0.4 and 1.1 ng·mL−1 after repeated boluses. In the infusion group, the cortex, thalamus and cerebellum oxycodone concentrations were 4‐8 times higher and in the spinal cord 1310 times higher than in plasma. In the repeated boluses group, brain tissue concentrations were similar in the three areas, and in the spinal cord were 720 times higher than in plasma. Oxymorphone was the main metabolite detected, which accumulated in the brain and spinal cord tissue. In conclusion, first, accumulation of oxycodone and oxymorphone in the CNS was observed, and second, high spinal cord concentrations suggest that epidural oxycodone may provide segmental analgesia.
Basic & clinical pharmacology & toxicology
|Pages:||430 - 438|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3126 Surgery, anesthesiology, intensive care, radiology
This work was supported by Olvi Foundation, Iisalmi, Finland, and the Finnish Cultural Foundation, Helsinki, Finland.
© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). This is the peer reviewed version of the following article: Kinnunen, M, Kokki, H, Hautajärvi, H, et al. Oxycodone concentrations in the central nervous system and cerebrospinal fluid after epidural administration to the pregnant ewe. Basic Clin Pharmacol Toxicol. 2019; 125: 430– 438. https://doi.org/10.1111/bcpt.13276, which has been published in final form at https://doi.org/10.1111/bcpt.13276. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.