Pharmacokinetics and safety of inhaled oxytocin compared with intramuscular oxytocin in women in the third stage of labour: A randomized open-label study

Katarzyna Gajewska-Knapik, Subramanya Kumar, Amy Sutton-Cole, Kirsten R. Palmer, Anthony Cahn, Rachel A. Gibson, Carl Kirkpatrick, Simon Parry, Ian Schneider, Sarah Siederer, Annie Stylianou, Kimberley Hacquoil, Marcy Powell, Melissa Ellis, Michelle P. McIntosh, Pete Lambert

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Aims: To compare pharmacokinetics (PK) and safety of heat-stable inhaled (IH) oxytocin with intramuscular (IM) oxytocin in women in third stage of labour (TSL), the primary endpoint being PK profiles of oxytocin IH and secondary endpoint of safety. Methods: A phase 1, randomized, cross-over study was undertaken in 2 UK and 1 Australian centres. Subjects were recruited into 2 groups: Group 1, women in TSL; Group 2, nonpregnant women of childbearing potential (Cohort A, combined oral contraception; Cohort B, nonhormonal contraception). Participants were randomized 1:1 to: Group 1, oxytocin 10 IU (17 μg) IM or oxytocin 240 IU (400 μg) IH immediately after delivery; Group 2, oxytocin 5 IU (8.5 μg) intravenously and oxytocin 240 IU (400 μg) IH at 2 separate dosing sessions. Results: Participants were recruited between 23 November 2016 to 4 March 2019. In Group 1, 17 participants were randomized; received either IH (n = 9) or IM (n = 8) oxytocin. After IH and IM administration, most plasma oxytocin concentrations were below quantification limits (2 pg/mL). In Group 2 (n = 14), oxytocin IH concentrations remained quantifiable ≤3 h postdose. Adverse events were reported in both groups, with no deaths reported: Group 1, IH n = 3 (33%) and IM n = 2 (25%); Group 2, n = 14 (100%). Conclusion: Safety profiles of oxytocin IH and IM were similar. However, PK profiles could not be established for oxytocin IH or IM in women in TSL, despite using a highly sensitive and specific assay.

Original languageEnglish
Pages (from-to)3681-3689
Number of pages9
JournalBritish Journal of Clinical Pharmacology
Volume89
Issue number12
DOIs
Publication statusPublished - Dec 2023

Keywords

  • obstetric haemorrhage
  • oxytocin
  • pharmacokinetics
  • randomized clinical trial

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