Oxycodone pharmacokinetics and fetal exposure after intravenous or epidural administration to the ewe

Mari Kinnunen, Hannu Kokki, Heidi Hautajärvi, Heikki Huhta, Veli Pekka Ranta, Juha Rasanen, Hanna Marja Voipio, Merja Kokki

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Introduction: There are limited data on oxycodone pharmacokinetics during pregnancy and on fetal exposure after maternal administration. The present study describes the pharmacokinetics of intravenous (i.v.) oxycodone in pregnant sheep and fetal exposure after intravenous and epidural administration. Material and methods: Ten pregnant sheep received 0.1 mg·kg−1 oxycodone intravenously, and blood samples were collected up to 24 hours. Seven days later, the ewes were randomized to receive 0.5 mg·kg−1 oxycodone intravenously (n = 5) or epidurally (n = 5) as a single bolus, before laparotomy for placement of catheters into the fetal superior vena cava and carotid artery. Paired maternal and fetal blood samples were taken when the fetal arterial catheter was in place and at the end of surgery. Maternal blood samples were taken up to 24 hours. Results: After 0.1 mg·kg−1 oxycodone intravenously, the median clearance was 5.2 L·h−1·kg−1 (range 4.6-6.2), but the volume of distribution varied between 1.5 and 4.7 L·kg−1. The area under the curve was 17 h·ng·mL−1 (range 14-19) and the plasma concentration at 2 minutes 60 ng·mL−1 (range 50-74). Following administration of 0.5 mg·kg−1 intravenously or epidurally, oxycodone concentrations were similar in the maternal and the fetal plasma. Accumulation of oxymorphone in the fetus occurred; fetal-to-maternal ratios were 1.3-3.5 (median 2.1) in the i.v.-group and 0.9-3.0 (1.3) in the Epidural-group. Conclusions: We determined the pharmacokinetics of oxycodone in pregnant sheep. We showed accumulation of oxymorphone, which an active metabolite of oxycodone, in the fetus. Further studies in human pregnancies are required to evaluate the safety of oxycodone.

Original languageEnglish (US)
Pages (from-to)1200-1205
Number of pages6
JournalActa Obstetricia et Gynecologica Scandinavica
Volume97
Issue number10
DOIs
StatePublished - Oct 1 2018
Externally publishedYes

Fingerprint

Oxycodone
Pharmacokinetics
Oxymorphone
Mothers
Sheep
Fetus
Catheters
Maternal Exposure
Pregnancy
Superior Vena Cava
Fetal Blood
Carotid Arteries
Intravenous Administration
Laparotomy
Area Under Curve
Safety

Keywords

  • analgesia
  • fetus
  • oxycodone
  • oxymorphone
  • pharmacokinetics
  • pregnancy

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Kinnunen, M., Kokki, H., Hautajärvi, H., Huhta, H., Ranta, V. P., Rasanen, J., ... Kokki, M. (2018). Oxycodone pharmacokinetics and fetal exposure after intravenous or epidural administration to the ewe. Acta Obstetricia et Gynecologica Scandinavica, 97(10), 1200-1205. https://doi.org/10.1111/aogs.13378

Oxycodone pharmacokinetics and fetal exposure after intravenous or epidural administration to the ewe. / Kinnunen, Mari; Kokki, Hannu; Hautajärvi, Heidi; Huhta, Heikki; Ranta, Veli Pekka; Rasanen, Juha; Voipio, Hanna Marja; Kokki, Merja.

In: Acta Obstetricia et Gynecologica Scandinavica, Vol. 97, No. 10, 01.10.2018, p. 1200-1205.

Research output: Contribution to journalArticle

Kinnunen, M, Kokki, H, Hautajärvi, H, Huhta, H, Ranta, VP, Rasanen, J, Voipio, HM & Kokki, M 2018, 'Oxycodone pharmacokinetics and fetal exposure after intravenous or epidural administration to the ewe', Acta Obstetricia et Gynecologica Scandinavica, vol. 97, no. 10, pp. 1200-1205. https://doi.org/10.1111/aogs.13378
Kinnunen, Mari ; Kokki, Hannu ; Hautajärvi, Heidi ; Huhta, Heikki ; Ranta, Veli Pekka ; Rasanen, Juha ; Voipio, Hanna Marja ; Kokki, Merja. / Oxycodone pharmacokinetics and fetal exposure after intravenous or epidural administration to the ewe. In: Acta Obstetricia et Gynecologica Scandinavica. 2018 ; Vol. 97, No. 10. pp. 1200-1205.
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AU - Hautajärvi, Heidi

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AU - Ranta, Veli Pekka

AU - Rasanen, Juha

AU - Voipio, Hanna Marja

AU - Kokki, Merja

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N2 - Introduction: There are limited data on oxycodone pharmacokinetics during pregnancy and on fetal exposure after maternal administration. The present study describes the pharmacokinetics of intravenous (i.v.) oxycodone in pregnant sheep and fetal exposure after intravenous and epidural administration. Material and methods: Ten pregnant sheep received 0.1 mg·kg−1 oxycodone intravenously, and blood samples were collected up to 24 hours. Seven days later, the ewes were randomized to receive 0.5 mg·kg−1 oxycodone intravenously (n = 5) or epidurally (n = 5) as a single bolus, before laparotomy for placement of catheters into the fetal superior vena cava and carotid artery. Paired maternal and fetal blood samples were taken when the fetal arterial catheter was in place and at the end of surgery. Maternal blood samples were taken up to 24 hours. Results: After 0.1 mg·kg−1 oxycodone intravenously, the median clearance was 5.2 L·h−1·kg−1 (range 4.6-6.2), but the volume of distribution varied between 1.5 and 4.7 L·kg−1. The area under the curve was 17 h·ng·mL−1 (range 14-19) and the plasma concentration at 2 minutes 60 ng·mL−1 (range 50-74). Following administration of 0.5 mg·kg−1 intravenously or epidurally, oxycodone concentrations were similar in the maternal and the fetal plasma. Accumulation of oxymorphone in the fetus occurred; fetal-to-maternal ratios were 1.3-3.5 (median 2.1) in the i.v.-group and 0.9-3.0 (1.3) in the Epidural-group. Conclusions: We determined the pharmacokinetics of oxycodone in pregnant sheep. We showed accumulation of oxymorphone, which an active metabolite of oxycodone, in the fetus. Further studies in human pregnancies are required to evaluate the safety of oxycodone.

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