A study of the pharmacokinetics and pharmacodynamics of oxytocin at elective caesarean delivery

D T Monks; P M Singh; L Kagan; A Palanisamy

doi:10.1111/anae.16109

A study of the pharmacokinetics and pharmacodynamics of oxytocin at elective caesarean delivery

Anaesthesia. 2023 Nov;78(11):1347-1353. doi: 10.1111/anae.16109. Epub 2023 Aug 18.

Authors

D T Monks¹, P M Singh¹, L Kagan², A Palanisamy¹

Affiliations

¹ Division of Obstetric Anesthesiology, Department of Anaesthesiology, Washington University School of Medicine in Saint Louis, MO, USA.
² Department of Pharmaceutics, Director Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy Rutgers, The State University of New Jersey, Piscataway, NJ, USA.

PMID: 37594215
DOI: 10.1111/anae.16109

Abstract

Oxytocin is widely used to prevent atonic postpartum haemorrhage after caesarean delivery. Initial treatment failure rates are high and inadequate dosing may contribute. Excessive doses, however, are associated with serious adverse effects. The pharmacokinetic data from this context are sparse and there is a lack of data in the immediate postpartum minutes after an initiating bolus. The pharmacodynamic data from this context are exclusively from dose-effect studies, with some suggesting that higher doses of oxytocin are required to provide adequate uterine tone in obese compared with non-obese women. We aimed to perform a pharmacokinetic and pharmacodynamic study that would facilitate more precise weight-based oxytocin dosing. We measured arterial oxytocin concentration, uterine tone and haemodynamic parameters in 25 women in the first 40 min after exogenous oxytocin administration at elective caesarean delivery. Serum oxytocin concentrations varied considerably between individuals. We constructed a one-compartment pharmacokinetic model of exogenous oxytocin deposition, after its administration with an initiating bolus and a maintenance infusion, at elective caesarean delivery. Body weight was evaluated as a potential covariate but was not included in the model due to lack of statistically significant reduction in the objective function. We calculated the volume of distribution and clearance (mean [coefficient of variation]) as 156.1 l [18%] and 83 ml.s^-1 [32%] but found no within-individual correlation between serum oxytocin concentration and uterine tone or haemodynamic parameters. In conclusion, we observed a large variation in serum oxytocin concentrations between individuals receiving similar doses of oxytocin and were unable to establish weight-based dosing of exogenous oxytocin at caesarean delivery. Our findings suggest that future studies on oxytocin pharmacokinetics would need large sample sizes. In the absence of such data, oxytocin dosing should continue to be guided by uterine tone assessments and adjusted according to a strategy based on the best evidence from dose-effect studies.

Keywords: caesarean; oxytocin; pharmacodynamics; pharmacokinetics.