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

Abstract

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. 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 10IU (17 μg) IM or oxytocin 240 IU (400 μg) IH immediately after delivery; Group 2, oxytocin 5IU (8.5μg) intravenously and oxytocin 240 IU (400 μg) IH at 2 separate dosing sessions. 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 (2pg/mL). In Group 2 (n= 14), oxytocin IH concentrations remained quantifiable ≤3h 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%). 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.