Disposition of Intravenous Paracetamol in Young Women

Universitaire Ziekenhuizen KU Leuven

Status: Completed

Conditions: Pain

Treatments: Drug: intravenous paracetamol (acetaminophen)

Study type: Observational

Funder types: Other

Identifiers

NCT02590900

ML6563

Details and patient eligibility

About

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.

Full description

This study aims to perform a pooled analysis of:

1. 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).
2. 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)
3. A dataset in 8 young women not on oral contraceptives, iv paracetamol, single dose.

Enrollment: 69 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. informed consent
2. for patients (pregnant women at delivery), there has to be a clinical indication (post caesarean analgesia, NPO) to administer iv paracetamol.

Exclusion criteria

1. intolerance to paracetamol
2. withdrawal of informed consent.

Trial design

69 participants in 3 patient groups

at delivery

Description:

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.

Treatment:

Drug: intravenous paracetamol (acetaminophen)

postpartum

Description:

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

Treatment:

Drug: intravenous paracetamol (acetaminophen)

healthy female volunteers

Description:

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.

Treatment:

Drug: intravenous paracetamol (acetaminophen)