Introduction: Poor intra-operative blood pressure is a risk factor for kidney, heart, and cognitive post-operative complications. Literature suggests that use of low-dose peripheral norepinephrine (NOR) reduces organ dysfunction, yet its administration remains unstandardized. In this work we develop a pharmacokinetic/pharmacodynamics (PK/PD) model of NOR effect on mean arterial pressure (mAP). Methods: From June 2018 to December 2021, we included patients scheduled for elective neurosurgery and requiring vasopressors for intra-operative hypotension management at Lariboisière Hospital, Paris. Low doses of NOR were administered peripherally, and successive arterial blood samples were collected to track its plasmatic concentration. We used a compartmental modelling approach for NOR PK. We developed and compared two models for NOR PD on mAP. Model comparison was done using Bayes information criteria. The resulting PK/PD model parameters were fitted over the entire population and linked to age, weight, height and sex. Results: We included 29 patients (age 52[46-64] years, 69% female). NOR median time to peak effect on mAP was 74[53-94] seconds. After bolus administration, mAP increased by 24% [15 - 31]. A 3-comparments model best captured NOR PK. NOR PD effect on mAP was well represented by both Emax and Windkessel models, with better results for the former. We found that age, height and weight as well as history of smoking and hypertension were correlated with model parameters. Conclusions: We developed a PK/PD model to accurately track norepinephrine plasma concentration and its effect on mAP over time, which could serve for target-controlled infusion. Study registration: ClinicalTrials.gov (NCT03454204)