Paracetamol glucuronidation microdosing
Conditions
Interventions
If the probe drug (paracetamol) is given IV for clinical therapy at a therapeutic
dose, a 14C-labeled-paracetamol microdose will be given simultaneously orally.
Sponsors
Erasmus MC
Eligibility
Inclusion criteria
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
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 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,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma paracetamol to APAP-glucuronide clearance, as surrogate marker of UGT activity in vivo | — |
Secondary
| Measure | Time frame |
|---|---|
| The following parameters will be estimated for both formulations: paracetamol and metabolite plasma and urinary clearance, volume of distribution, AUC, Cmax, Tmax, plasma and urinary APAP-glu/APAP-sulfate ratio. Oral bioavailability of paracetamol. In feces: paracetamol and metabolite appearance. Description of the feasibility of a microdosing study in a pediatric population. | — |
Contacts
Public ContactS.N. Wildt, de
Erasmus MC
Outcome results
None listed