Pediatric microdosing: elucidating age-related changes in oral absorptio

Completed

Conditions: ontogenie van medicamenteuze intestinale absorptie en metabolisme
age related changes in drug metabolism and absorption

Registration Number: NL-OMON39097

Lead Sponsor: Erasmus MC, Universitair Medisch Centrum Rotterdam

Brief Summary: Trial ended prematurely

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 32

Inclusion Criteria

Age 0 to 6 years inclusive
At least 32 weeks of post conceptual age
Intravenous or intra-arterial access for blood sampling in place
Receiving paracetamol IV
Parental informed consent

Exclusion Criteria

Anticipated death in 48 hours
No informed consent
ECMO treatment
Circulatory failure:
- receiving more than 1 vasopressor or
- increase of vasopressor drug dose in the last 6 hours
Renal disorders
- In need of renal dialysis
- Estimated risk for kidney injury or failure at least 'risk for renal dysfunction' according to pRIFLE criteria. Which means an estimated creatinine clearance decreased by 25% or more, or urine output of <0.5mL/kg per hour for 8 hours.
Hepatic failure:
- >2SD in age appropriate liver enzymes measurement (ASAT and ALAT)
Gastrointestinal disorders
- Ileus, diarrhea, short bowel disease, underlying inflammatory bowel disease, pancreatic insufficency, (e.g. cystic fibrosis), celiac disease
Use of co-medication known to affect paracetamol metabolism (according to the Farmacotherapeutische Kompas, www.fk.cvz.nl)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. Plasma paracetamol to APAP-glucuronide clearance, as surrogate marker of UGT<br /><br>activity in vivo</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secundary outcomes are:<br /><br>1. The following parameters will be estimated for both formulations:<br /><br>paracetamol and metabolite plasma and urinary clearance, volume of<br /><br>distribution, AUC, Cmax, Tmax, plasma and urinary APAP-glu/APAP-sulfate ratio.<br /><br>Oral bioavailability of paracetamol. In feces: paracetamol and metabolite<br /><br>appearance.<br /><br>Metabolites to be studied: Paracetamol-glucuronide (APAP-glu),<br /><br>paracetamol-4-hydroxysulfate (4-O-Sul), paracetamol-3-hydroxysulfate (3-O-Sul),<br /><br>paracetamol-3-cysteine (Cys), paracetamol-3-N-acetylcysteïne (Mer).<br /><br>2. Description of the feasibility of a microdosing study in a pediatric<br /><br>population.</p><br>