Proposal of a new limited sampling strategy to predict CYP3A activity using a partial AUC of midazolam

International audienc

Tactile sensor for correct endotracheal tube placement

We present a new device for verifying endotracheal tube position that uses specialized sensors to distinguish anatomical features of the trachea and esophagus. This device will increase the safety of resuscitation, surgery, and mechanical ventilation and decrease the morbidity, mortality, and health care costs associated with esophageal intubation and unintended extubation by improving the process and maintenance of endotracheal intubation. The device consists of a tactile sensor connected to the airway occlusion cuff that can detect the presence/absence of the tracheal rings.status: publishe

A novel airway device with tactile sensing capabilities for verifying correct endotracheal tube placement

We present a new device for verifying endotracheal tube (ETT) position that uses specialized sensors intended to distinguish anatomical features of the trachea and esophagus. This device has the potential to increase the safety of resuscitation, surgery, and mechanical ventilation and decrease the morbidity, mortality, and health care costs associated with esophageal intubation and unintended extubation by potentially improving the process and maintenance of endotracheal intubation. The device consists of a tactile sensor connected to the airway occlusion cuff of an ETT. It is intended to detect the presence or absence of tracheal rings immediately upon inflation of the airway occlusion cuff. The initial study detailed here verifies that a prototype device can detect contours similar to tracheal rings in a tracheal model.status: publishe

Microfluidic-based measurements of cytochrome P450 enzyme activity of primary mammalian hepatocytes

A microfluidic-based system was developed for the in situ monitoring of the 7-ethoxyresorufin O-dealkylation (EROD) activity of primary rat hepatocytes by measuring the fluorescent intensity of both cells and their surrounding media. The microfluidic chip was designed to allow the cell suspension and test reagent to be introduced in a layer-by-layer flow format, thereby resulting in a short mixing time by diffusion. A good linear relationship was obtained between the resorufin concentration up to 30 M and fluorescent intensity over the chip's circular chamber area. The EROD activity was determined with 3-methylcholanthrene (3-MC)-induced hepatocytes. The inhibition effect of -naphthoflavone was also examined on EROD activity resulting in an IC50 value of 12.98 M

Pharmacokinetics of intravenous and oral midazolam in plasma and saliva in humans: usefulness of saliva as matrix for CYP3A phenotyping

AIMS: To compare midazolam kinetics between plasma and saliva and to find out whether saliva is suitable for CYP3A phenotyping. METHODS: This was a two way cross-over study in eight subjects treated with 2 mg midazolam IV or 7.5 mg orally under basal conditions and after CYP3A induction with rifampicin. RESULTS: Under basal conditions and IV administration, midazolam and 1'-hydroxymidazolam (plasma, saliva), 4-hydroxymidazolam and 1'-hydroxymidazolam-glucuronide (plasma) were detectable. After rifampicin, the AUC of midazolam [mean differences plasma 53.7 (95% CI 4.6, 102.9) and saliva 0.83 (95% CI 0.52, 1.14) ng ml(-1) h] and 1'-hydroxymidazolam [mean difference plasma 11.8 (95% CI 7.9 , 15.7) ng ml(-1) h] had decreased significantly. There was a significant correlation between the midazolam concentrations in plasma and saliva (basal conditions: r = 0.864, P > 0.0001; after rifampicin: r = 0.842, P > 0.0001). After oral administration and basal conditions, midazolam, 1'-hydroxymidazolam and 4-hydroxymidazolam were detectable in plasma and saliva. After treatment with rifampicin, the AUC of midazolam [mean difference plasma 104.5 (95% CI 74.1, 134.9) ng ml(-1) h] and 1'-hydroxymidazolam [mean differences plasma 51.9 (95% CI 34.8, 69.1) and saliva 2.3 (95% CI 1.9, 2.7) ng ml(-1) h] had decreased significantly. The parameters separating best between basal conditions and post-rifampicin were: (1'-hydroxymidazolam + 1'-hydroxymidazolam-glucuronide)/midazolam at 20-30 min (plasma) and the AUC of midazolam (saliva) after IV, and the AUC of midazolam (plasma) and of 1'-hydroxymidazolam (plasma and saliva) after oral administration. CONCLUSIONS: Saliva appears to be a suitable matrix for non-invasive CYP3A phenotyping using midazolam as a probe drug, but sensitive analytical methods are required