Pediatric Microdosing paracetamol: elucidating age-relatedchanges in oral drug absorptio

Completed

Conditions: Paracetamol glucuronidation microdosing

Registration Number: NL-OMON23846

Lead Sponsor: Erasmus MC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 60

Inclusion Criteria

Patients need to fulfil all of the following 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
 Estimated risk for kidney injury or failure at least ‘risk for renal dysfunction’
according to pRIFLE criteria. Which means an estimated creatinine clearancedecreased by 25% or more, or urine output of <0.5 mL/kg per hour for 8
hours.
 In need of renal dialysis
- Hepatic failure
 >2SD in age appropriate liver enzyme measurement (ASAT and ALAT)
- Gastrointestinal disorders
Ileus, diarrhea, short bowel disease, underlying inflammatory bowel disease,
pancreatic insufficiency (e.g. cystic fibrosis), celiac disease
- Use of co-medication known to affect paracetamol metabolism (according to the
Farmacotherapeutische Kompas, www.fk.cvz.nl, and Micromedex,

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
The following parameters will be estimated for both formulations: paracetamol and<br>metabolite plasma and urinary clearance, volume of distribution, AUC, Cmax, Tmax, plasma and urinary APAP-glu/APAP-sulfate ratio. Oral bioavailability of paracetamol.<br>In feces: paracetamol and metabolite appearance.<br><br>Description of the feasibility of a microdosing study in a pediatric population.<br>