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Oxycodone concentrations in the central nervous system and cerebrospinal fluid after epidural administration to the pregnant ewe.
Basic Clin Pharmacol Toxicol 2019; 125(5):430-438BC

Abstract

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.

Authors+Show Affiliations

School of Medicine, University of Eastern Finland, Kuopio, Finland.School of Medicine, University of Eastern Finland, Kuopio, Finland.Admescope Ltd, Oulu, Finland.Department of Obstetrics and Gynaecology, Oulu University Hospital and University of Oulu, Oulu, Finland.Department of Obstetrics and Gynaecology, Oulu University Hospital and University of Oulu, Oulu, Finland. Department of Obstetrics and Gynaecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.Laboratory Animal Centre, Department of Experimental Surgery, Oulu University Hospital and University of Oulu, Oulu, Finland.Department of Anaesthesia and Intensive Care, Kuopio University Hospital, Kuopio, Finland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31222944

Citation

Kinnunen, Mari, et al. "Oxycodone Concentrations in the Central Nervous System and Cerebrospinal Fluid After Epidural Administration to the Pregnant Ewe." Basic & Clinical Pharmacology & Toxicology, vol. 125, no. 5, 2019, pp. 430-438.
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(5):430-438.
Kinnunen, M., Kokki, H., Hautajärvi, H., Lantto, J., Räsänen, J., Voipio, H. M., & Kokki, M. (2019). Oxycodone concentrations in the central nervous system and cerebrospinal fluid after epidural administration to the pregnant ewe. Basic & Clinical Pharmacology & Toxicology, 125(5), pp. 430-438. doi:10.1111/bcpt.13276.
Kinnunen M, 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(5):430-438. PubMed PMID: 31222944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxycodone concentrations in the central nervous system and cerebrospinal fluid after epidural administration to the pregnant ewe. AU - Kinnunen,Mari, AU - Kokki,Hannu, AU - Hautajärvi,Heidi, AU - Lantto,Juulia, AU - Räsänen,Juha, AU - Voipio,Hanna-Marja, AU - Kokki,Merja, Y1 - 2019/07/11/ PY - 2019/04/15/received PY - 2019/06/06/accepted PY - 2019/6/22/pubmed PY - 2019/6/22/medline PY - 2019/6/22/entrez KW - Analgesia KW - epidural KW - opioid KW - oxycodone KW - pharmacokinetics SP - 430 EP - 438 JF - Basic & clinical pharmacology & toxicology JO - Basic Clin. Pharmacol. Toxicol. VL - 125 IS - 5 N2 - 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. SN - 1742-7843 UR - https://www.unboundmedicine.com/medline/citation/31222944/Oxycodone_concentrations_in_the_central_nervous_system_and_cerebrospinal_fluid_after_epidural_administration_to_the_pregnant_ewe L2 - https://doi.org/10.1111/bcpt.13276 DB - PRIME DP - Unbound Medicine ER -