Pediatric microdosing midazolam: elucidating age-related changes in oral drug absorptio

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 60

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

- 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 <0.3 ml/kg/h for 24h or anuric for 12 hours.
- Acute liver failure AST/ALT >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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>1. Apparent clearance of midazolam (CL/F) to 1-OH-midazolam and<br /><br>4-OH-midazolam. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>2. Following parameters will be estimated for both formulations (IV and PO): Cl<br /><br>and Vd of midazolam and metabolites in plasma and urine in relation to age and<br /><br>PELOD score. For oral midazolam also: AUC, Cmax, Tmax,<br /><br>Metabolites: 1-OH-midazolam (1-OHM), 1-OH-midazolam-glucuronide (1-OHMG),<br /><br>4-OH-midazolam (4-OHM) 4-OH-midazolam-glucuronide (4-OHMG),<br /><br>Midazolam-glucuronide (M-G)<br /><br>In feces: midazolam and metabolite appearance<br /><br>3. Description of feasibility of microdosing study in pediatric population.<br /><br>4. Metabolic profile of oral midazolam in pediatric population.</p><br>