s-1743 and Brain-Injuries

Thiopental is a thiobarbiturate given in the case of brain injuries to reduce intracranial pressure and to manage cerebral ischemia. A pharmacokinetic model has been described previously in critically ill patients with a different therapeutic strategy. New treatment options prompted us to investigate if drug-drug interactions occur. A new model is proposed describing the influence of concomitant administration of esomeprazole on the distribution of thiopental.. The study population comprised 52 critically ill patients (body weight 47.1-114 kg) aged 18-78 years who had been admitted into the critical care unit for treatment of intracranial hypertension. A total mean dose of 282.8 ± 172.7 mg/kg was given in 96 ± 72 h. Pharmacokinetic analysis was performed by using a nonlinear mixed-effect population model.. A one-compartment open model with first-order elimination identified two covariates, namely, body weight on clearance and volume of distribution, and the administration of esomeprazole on volume of distribution. The mean values (% relative standard error) for total clearance (CL) and for central volume of distribution (Vd) in patients with and without concomitant esomeprazole were 5.3 L/h (9.2 %) and 256.1 (6.4 %) and 153.2 l (19.2 %), respectively.. Based on these results, we conclude that concomitant administration of esomeprazole increases the volume of distribution and the half-live of thiopental. This drug-drug interaction should be considered when a target concentration has to be reached.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Brain Injuries; Critical Illness; Drug Interactions; Esomeprazole; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Models, Biological; Proton Pump Inhibitors; Thiopental; Young Adult

To explore the protective effect of esomeprazole upon stress-related intestinal mucosal damage following traumatic brain injury (TBI) in rats.. Male Wistar rats were randomly divided into three groups: groups A and B served as TBI models and group C was designated as a normal control (shame operation). In group B rats were treated subcutaneously with esomeprazole prior to TBI while groups A and C rats were treated with an equivalent amount of normal saline. During the observation period, the morphological changes of brain tissue and intestinal mucosa were observed. And the intestinal mucosal permeability to fluorescein isothiocyanate (FITC)-labeled dextran and diamine oxidase (DAO) activity were assessed. The activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and the levels of malondialdehyde (MDA), reduced glutathione (GSH) and hydroxyl radical (OH(*)) were measured.. (1) During the observation period of TBI, the intestinal mucosal was damaged, but there was improvement in group PPI. (2) FITC-dextran leakage increased after TBI and peaked at 24 h (P < 0.01); its level of (3720 +/- 401) ng/ml in group PPI was lower than that in group TBI (5230 +/- 489) ng/ml (P < 0.05). (3) The DAO activity in mucosa decreased and the decline was the greatest at 24 h (P < 0.05), its level of (0.44 +/- 0.11) ng/ml in group PPI at 24 h was higher than that in group TBI (0.31 +/- 0.07) ng/ml (P < 0.05); while the DAO activity in serum increased significantly. (4) The activity of SOD and the level of GSH in intestinal mucosal started to decrease at 3 h and the decline was the greatest at 24 h (P < 0.05), their levels were (10.2 +/- 2.8) U/mgprot and (140 +/- 46) mg/gprot respectively in group TBI, a remarkable drop in comparison with those of PPI group (13.0 +/- 2.4) U/mgprot and (208 +/- 48) U/gprot (P < 0.05). (5) The levels of OH(.), MDA and MPO in intestinal mucosal increased and peaked at 24 h (P < 0.05), the respective levels in group PPI (108 +/- 8), (6.2 +/- 0.6) and (1.53 +/- 0.52) U/mgprot and those in the TBI group (150 +/- 8), (7.7 +/- 0.9), (1.93 +/- 0.53) U/mgprot, demonstrated that there was a remarkable rise (P < 0.05).. Traumatic brain injury may lead to stress-related intestinal mucosal damage. Oxygen free radicals play an important role in intestinal mucosal barrier damage. Esomeprazole attenuates the damage of intestinal mucosal barrier by antioxidant effect and inhibiting the activity of neutrophil.

Topics: Animals; Brain Injuries; Esomeprazole; Free Radicals; Intestinal Absorption; Intestinal Mucosa; Intestines; Male; Rats; Rats, Wistar; Reactive Oxygen Species