Disposition of Intravenous Paracetamol in Young Women
Disposition of Intravenous Paracetamol in Young Women, Including During Pregnancy, in Postpartum or When on Oral Contraceptives
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
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at delivery
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.
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paracetamol disposition in young women, exploring the impact of covariates (pregnancy, postpartum, oral contraceptives) in this population.
Otros nombres:
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postpartum
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
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paracetamol disposition in young women, exploring the impact of covariates (pregnancy, postpartum, oral contraceptives) in this population.
Otros nombres:
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healthy female volunteers
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. |
paracetamol disposition in young women, exploring the impact of covariates (pregnancy, postpartum, oral contraceptives) in this population.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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paracetamol disposition in young women: total clearance and metabolite specific clearance estimates
Periodo de tiempo: 24 h is the maximal time frame of this pharmacokinetic study (PK is the outcome measured
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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)
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24 h is the maximal time frame of this pharmacokinetic study (PK is the outcome measured
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: karel allegaert, MD, PhD, Universitaire Ziekenhuizen KU Leuven
Publicaciones y enlaces útiles
Publicaciones Generales
- Beleyn B, Vermeersch S, Kulo A, Smits A, Verbesselt R, de Hoon JN, Van Calsteren K, Allegaert K. Estradiol and weight are covariates of paracetamol clearance in young women. Gynecol Obstet Invest. 2014;77(4):211-6. doi: 10.1159/000358394. Epub 2014 Mar 25.
- Kulo A, Peeters MY, Allegaert K, Smits A, de Hoon J, Verbesselt R, Lewi L, van de Velde M, Knibbe CA. Pharmacokinetics of paracetamol and its metabolites in women at delivery and post-partum. Br J Clin Pharmacol. 2013 Mar;75(3):850-60. doi: 10.1111/j.1365-2125.2012.04402.x.
- Gregoire N, Hovsepian L, Gualano V, Evene E, Dufour G, Gendron A. Safety and pharmacokinetics of paracetamol following intravenous administration of 5 g during the first 24 h with a 2-g starting dose. Clin Pharmacol Ther. 2007 Mar;81(3):401-5. doi: 10.1038/sj.clpt.6100064.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- ML6563
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