intestinale absorptie en metabolisme van geneesmiddelen bij kritisch zieke kinderen Intestinal drug absorption and metabolism in critically ill children
Conditions
Interventions
A single oral 14C-labelled-midazolam microdose 20ng/kg will be given.
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
2 Years to 11 Years
Inclusion criteria
Inclusion criteria: - Age 0 to 6 years inclusive - At least 36 weeks of post conceptual age or body weight 2.5 kg or more - Receiving midazolam IV - Parental informed consent - Intravenous or intra-arterial access for blood sampling
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 failure according to the pRIFLE criteria, i.e. estimated creatinine clearance decreased by 75% or an urine output of 2 times the upper limit for age - Gastrointestinal disorders Ileus, diarrhoea, short bowel disease, underlying inflammatory bowel disease, pancreatic insufficiency (e.g. cystic fibrosis), celiac disease. - Use of most relevant co-medication known to affect midazolam metabolism (according to the *Cytochrome P450 Drug Interactions Table*, listed in appendix 1) ;INHIBITORS Indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem, cimetidine , amiodarone, chloramphenicol, ciprofloxacin, delaviridine, diethyldithiocarbamate, fluvoxamine, gestodene, imatinib, mibefradil, mifepristone, norfloxacin, norfluoxetine, star fruit, voriconazole INDUCERS Efavirenz, nevirapine, barbiturates, carbamazepine, efavirenz, glucocorticoids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John*s wort, troglitazone
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Apparent clearance of midazolam (CL/F) to 1-OH-midazolam and 4-OH-midazolam. | — |
Secondary
| Measure | Time frame |
|---|---|
| 2. Following parameters will be estimated for both formulations (IV and PO): Cl and Vd of midazolam and metabolites in plasma and urine in relation to age and PELOD score. For oral midazolam also: AUC, Cmax, Tmax, Metabolites: 1-OH-midazolam (1-OHM), 1-OH-midazolam-glucuronide (1-OHMG), 4-OH-midazolam (4-OHM) 4-OH-midazolam-glucuronide (4-OHMG), Midazolam-glucuronide (M-G) In feces: midazolam and metabolite appearance 3. Description of feasibility of microdosing study in pediatric population. 4. Metabolic profile of oral midazolam in pediatric population. | — |
Countries
Netherlands
Outcome results
None listed