Midazolam, ontogeny, children, absoprtion, metabolism.
Conditions
Interventions
If the probe drug (midazolam) is given IV for clinical therapy at a therapeutic dose, a 14C-labeled-midazolam microdose will be given simultaneously orally.
Sponsors
Erasmus Medical Center
Eligibility
Inclusion criteria
Inclusion criteria: Age 0 to 6 years inclusive - At least 36 weeks of post conceptual age or bodyweight >2,5kg - Intravenous or intra-arterial access for blood sampling in place - Receiving midazolam 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. - Chronic liver cirrhosis or chronic renal failure - Renal disorders: Estimated risk for kidney injury or failure at least ‘risk for renal dysfunction’ according to pRIFLE criteria - Hepatic failure: >2SD in age appropriate liver enzyme measurement (ASAT and ALAT) - Gastrointestinal disorderse - Use of co-medication known to affect midazolam metabolism (according to the Farmacotherapeutische Kompas, www.fk.cvz.nl, and Micromedex)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma midazolam to midazolam and metabolite clearance, as surrogate marker of CYP3A activity in vivo | — |
Secondary
| Measure | Time frame |
|---|---|
| The following parameters will be estimated for both formulations: midazolam and metabolite plasma and urinary clearance, volume of distribution, AUC, Cmax, Tmax. In feces: midazolam and metabolite appearance. Oral bioavailability of midazolam. Description of the feasibility of a microdosing study in a pediatric population. | — |
Contacts
Public ContactS.N. Wildt, de
Erasmus MC
Outcome results
None listed