TY - JOUR
T1 - Pharmacokinetics and safety of inhaled oxytocin compared with intramuscular oxytocin in women in the third stage of labour
T2 - A randomized open-label study
AU - Gajewska-Knapik, Katarzyna
AU - Kumar, Subramanya
AU - Sutton-Cole, Amy
AU - Palmer, Kirsten R.
AU - Cahn, Anthony
AU - Gibson, Rachel A.
AU - Kirkpatrick, Carl
AU - Parry, Simon
AU - Schneider, Ian
AU - Siederer, Sarah
AU - Stylianou, Annie
AU - Hacquoil, Kimberley
AU - Powell, Marcy
AU - Ellis, Melissa
AU - McIntosh, Michelle P.
AU - Lambert, Pete
N1 - Funding Information:
K.R.P. declares having received consulting fees from Janssen Pharmaceuticals and funding to her institution from GSK. S.K., A.C., R.A.G., A.S., M.P., M.E. and S.S. are employees of and hold stocks in GSK. S.P., I.S. and K.H. were employed by GSK at the time of the study. S.P. and I.S. hold stocks in GSK. M.P.M. declares having received research support from Janssen Pharmaceuticals, and grants/contracts from the Department of Education and Training, Victoria State Government (Smart Manufacturing and Technology Hub), the Victorian Medical Research Acceleration Fund, Department Jobs, Precincts and Regions, Victoria State Government (Clinical proof of concept for the inhaled oxytocin project), and the Medical Research Future Fund, Australian Government (Stroke – Prevention of Reperfusion Injury and Neuroinflammation – a Therapeutic Strategy: Medical Research Future Fund, Australian Government; Novel inhibitors of SARS coronaviruses targeting ACE2). M.P.M. also declared speaker honorarium for International Society for Aerosol Medicines Congress 2021, and is inventor on the patent method and formulation for oxytocin inhalation: McIntosh, M., D. Morton, T. Sou, L. Olerile and R. Prankerd (2014). US20140294969A1 ‐ WO2013/016754 A1 ‐ PCT/AU2011001430. These authors declare no other financial or nonfinancial relationships and activities. K.G.‐K., A.S.‐C., C.K. and P.L. declare no financial or nonfinancial relationships and activities and no conflicts of interest.
Publisher Copyright:
© 2023 GSK. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - obstetric haemorrhage
KW - oxytocin
KW - pharmacokinetics
KW - randomized clinical trial
UR - https://www.scopus.com/pages/publications/85169156522
U2 - 10.1111/bcp.15860
DO - 10.1111/bcp.15860
M3 - Article
C2 - 37485589
AN - SCOPUS:85169156522
SN - 0306-5251
VL - 89
SP - 3681
EP - 3689
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 12
ER -