Disposition of Intravenous Paracetamol in Young Women

Study Overview
=================
Brief Summary
-----------------
Compared to early postpartum (10-15 weeks) observations, paracetamol clearance was significantly higher (21.1 vs 11.7 l.h-1, + 80 %) at delivery. This higher clearance was due to a disproportional increase in glucuronidation (11.6 vs 4.76 l.h-1, + 144 %), a proportional increase in oxidation clearance (4.95 vs 2.77 l.h-1, 78 %) and primary renal clearance (1.15 vs 0.75 l.h-1, 53 %) [KUlo et al, Int J Obstet Anesth]. This increase in glucuronidation clearance may in part be driven by oestradiol, and may explain within and between individual differences in paracetamol metabolism (e.g. oral contraceptives, follicular vs luteal phase, postpartum, pregnancy, or duration of pregnancy) in young women. Based on a pooled analysis, investigators aimed to further explore the impact of these covariates on paracetamol metabolism based on plasma and urine collections in women at delivery, in postpartum (early, or late) and healthy volunteers, either or not on oral contraceptives (OC) following intravenous (iv) paracetamol administration.

Detailed Description
-----------------
This study aims to perform a pooled analysis of: Paracetamol PK data recently published in 47 pregnant women. In these cases, iv paracetamol was administered q6h after delivery (caesarean) for 24 h. 8 were recruited a second time for an additional single dose pK study in postpartum (Kulo et al, Br J Clin Pharmacol 2013). The PK data as initially published by Gregoire et al, but limited to female volunteers, all on oral contraceptives (n=14) (Gregoire et al, Clin Pharm Ther 2007) A dataset in 8 young women not on oral contraceptives, iv paracetamol, single dose.

Official Title
-----------------
Disposition of Intravenous Paracetamol in Young Women, Including During Pregnancy, in Postpartum or When on Oral Contraceptives

Conditions
-----------------
Pain

Intervention / Treatment
-----------------
* Drug: intravenous paracetamol (acetaminophen)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: informed consent for patients (pregnant women at delivery), there has to be a clinical indication (post caesarean analgesia, NPO) to administer iv paracetamol. Exclusion Criteria: intolerance to paracetamol withdrawal of informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| at delivery<br>women who underwent cesarean at delivery, and needed iv paracetamol as part of multimodal analgesia. In these cases, paracetamol was administered q6h (2g loading dose, 1g q6h for 24 h), and blood and urine samples were collected to describe paracetamol disposition at delivery. | Drug: intravenous paracetamol (acetaminophen)<br>* paracetamol disposition in young women, exploring the impact of covariates (pregnancy, postpartum, oral contraceptives) in this population.<br>* Other names: Perfusalgan, paracetamol Fresenius,;|
| postpartum<br>a subgroup of 8 women initially included in at delivery, underwent a second PK study 2-3 months postpartum and another PK study about 1 year after delivery. This PK study was based on a single iv paracetamol administration (2 g), and blood and urine samples were collected to describe paracetamol disposition in postpartum | Drug: intravenous paracetamol (acetaminophen)<br>* paracetamol disposition in young women, exploring the impact of covariates (pregnancy, postpartum, oral contraceptives) in this population.<br>* Other names: Perfusalgan, paracetamol Fresenius,;|
| healthy female volunteers<br>a group of 8 young healthy women not on oral contraceptives underwent a single PK study (2 g intravenous paracetamol) and blood and urine samples were collected to described paracetamol disposition in healthy female volunteers, not on oral contraceptives. Raw data as published by Gregoire et al (Clin Pharm Ther 2007) were available in 14 young women, all on contraceptives. | Drug: intravenous paracetamol (acetaminophen)<br>* paracetamol disposition in young women, exploring the impact of covariates (pregnancy, postpartum, oral contraceptives) in this population.<br>* Other names: Perfusalgan, paracetamol Fresenius,;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| paracetamol disposition in young women: total clearance and metabolite specific clearance estimates | pooled analysis of plasma and urine paracetamol and paracetamol metabolite data published in literature in young women following iv paracetamol administration. Samples (plasma and urine) will be collected in the 24 h time interval after initiation of intravenous paracetamol administration (time interval of the PK study) | 24 h is the maximal time frame of this pharmacokinetic study (PK is the outcome measured | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pharmacokinetics, pregnancy, oral contraceptives, oestradiol