Dosage Adjustment of Dabigatran Etexilate Based on Creatinine Clearance in Patients With Cardioembolic Stroke or Atrial Fibrillation.

BACKGROUND: A recommendation for dosage adjustment of dabigatran etexilate, a prodrug of dabigatran, seems to be desirable based on creatinine clearance to avoid bleeding and stroke. METHODS: Outpatients and inpatients having a history of cardioembolic stroke or atrial fibrillation were included. After taking dabigatran etexilate orally (75-150 mg twice daily) for at least 1 week, plasma trough concentration (Ctrough, ng/mL) of dabigatran and creatinine clearance (CLcr, mL/min) of patients according to Cockcroft and Gault equation were determined. RESULTS: Among the 38 patients studied, Ctrough of dabigatran and CLcr were scattered in a range from 31.4 to 329.5 ng/mL and 15.4-133.4 mL/min, respectively. Temporal CLtotal (Temp-CLtotal) of dabigatran, estimated by dividing the daily absorbed amount of dabigatran etexilate with Ctrough of dabigatran, was linearly correlated with CLcr of patients (P = 0.0018). Based on the findings, the daily dose of dabigatran etexilate that provides Ctrough of dabigatran at approximately 70 ng/mL was estimated. CONCLUSIONS: A linear relationship was found between Temp-CLtotal of dabigatran and CLcr of patients. Depending on CLxr of patients, we recommend 4 different dosages of dabigatran etexilate to obtain Ctrough of dabigatran at approximately 70 ng/mL.

Edema in the retropharyngeal space associated with head and neck tumors: CT imaging characteristics.

To determine computed tomographic (CT) imaging characteristics of retropharygeal edema, we reviewed CT images in 18 patients with head and neck tumors. Retropharyngeal edema spread craniocaudally between soft palate and upper half of thyroid cartilage in all patients. No edema fluid extended above soft palate and below thyroid cartilage. Horizontally, it spread symmetrically in ten and asymmetrically in eight patients. Predominance in asymmetrical retropharyngeal edema was found on the same side as that of unilateral predominance both in lymph nodes enlargement and jugular vein stenosis/occlusion. All patients had edema also in other cervical spaces. Edema of retropharyngeal and other spaces fluctuated synchronously. In 14 patients, as primary lesion and/or cervical lymph nodes regressed, retropharyngeal edema disappeared or decreased. Retropharyngeal edema had some imaging characteristics. With knowledge of that, we could avoid diagnostic confusion when evaluating head and neck CT images.

Prevention of irinotecan-induced diarrhoea by oral carbonaceous adsorbent (Kremezin) in cancer patients.

Irinotecan (CPT-11) treatments induce severe diarrhoea at a rate of >40%. In clinical trials, we evaluated the preventing effects of oral alkalization, which has been reported previously, and oral carbonaceous adsorbent (Kremezin trade mark ) on diarrhoea possibly induced by CPT-11. Evaluation was made by counting the maximum number of bowel motions in each patient. Five patients out of 7 treated with CPT-11 had bowel motions of >5 times daily, and maximum number of bowel motions reached 20 times in 1 patient. Oral alkalization (2 g sodium bicarbonate, 2 g magnesium oxide and 300 mg ursodeoxycholic acid daily for 4 days) decreased bowel motions from 20 to 8 thereafter in the patient. Maximum number of bowel motions in other 3 patients treated in a combination of CPT-11 and oral alkalization was <3. Oral adsorbent (2 g Kremezin x 3 times, during and after CPT-11 treatment) also decreased maximum number of bowel motions from 7 (without oral adsorbent) to 3 in 1 patient. Also, the maximum number of bowel motions in other 3 patients treated with oral adsorbent was <3 (p<0.05, vs CPT-11 alone). Effect of oral Kremezin on plasma concentrations of CPT-11 and its related compounds after a 1-h CPT-11 infusion, evaluated in a patient, was small. These results suggested that the oral Kremezin is effective in ameliorating CPT-11-induced diarrhoea without decreasing much the plasma clearance of CPT-11.

Acute superior mesenteric artery embolism: rapid reperfusion with hydrodynamic thrombectomy and pharmacological thrombolysis.

PURPOSE: To report a case of acute superior mesenteric artery (SMA) embolism successfully treated with hydrodynamic thrombectomy and pharmacological thrombolysis. CASE REPORT: A 67-year-old man was admitted to the hospital with acute severe abdominal pain. Selective angiography via a femoral puncture revealed a complete embolic occlusion distal to the first jejunal branch of the SMA. Hydrodynamic thrombectomy resolved the severe abdominal pain of the patient in approximately 10 minutes after the start of thrombectomy. Local continuous thrombolysis with urokinase resulted in near complete restoration of the mesenteric flow after 24 hours. The patient made an uneventful recovery and continues to do well on warfarin therapy 8 months after treatment; he has shown no evidence of malabsorption. CONCLUSIONS: Although insertion of the device into the SMA via a femoral puncture is a difficult approach, we propose that hydrodynamic thrombectomy followed by local thrombolysis is a useful treatment for acute superior mesenteric artery embolism.

Possible mechanism for pharmacokinetic interaction between lidocaine and mexiletine.

OBJECTIVE: Our objective was to elucidate the mechanism of pharmacokinetic interaction between lidocaine and mexiletine, because an unexpected increase in plasma lidocaine concentration accompanied by severe side effects was observed when mexiletine was administered to a patient with dilated cardiomyopathy. METHODS: Plasma concentrations of lidocaine, its major metabolites, and mexiletine were measured in a patient with dilated cardiomyopathy. The lidocaine-mexiletine interaction was evaluated by examination of the effects of mexiletine on plasma concentration and the tissue distribution of lidocaine in rabbits in vivo, as well as on the in vitro lidocaine binding to phosphatidylserine, a binding constituent for weakly basic drugs. RESULTS: Plasma lidocaine concentrations increased significantly when the oral dose of mexiletine was increased. This pharmacokinetic interaction was not attributable to a metabolic interaction as evaluated by plasma lidocaine metabolites concentrations. In rabbits, mexiletine seemed to decrease the total plasma clearance of lidocaine, resulting in increased plasma lidocaine concentrations. Mexiletine significantly reduced the tissue distribution of lidocaine to the kidneys and lungs. A strong displacing effect of mexiletine on the binding of lidocaine to phosphatidylserine was observed in vitro. CONCLUSIONS: A drug interaction derived from the displacement of lidocaine from tissue binding sites by mexiletine that resulted in the increased plasma lidocaine concentrations was shown. This observation had implications for loading doses and acute effects of lidocaine in the concurrent therapy of lidocaine and mexiletine.

[Effects of the volume and shape of voxels on the measurement of phantom volume using three-dimensional magnetic resonance imaging].

Recently, an increasing number of volumetric studies of the human brain have been reported, using three-dimensional magnetic resonance imaging (3D-MRI). To our knowledge, however, there are few investigations on the relation of the volume and shape of voxels which constitute an MR image to the accuracy in volume measurement of an imaged object. The purpose of this study was to evaluate the effect of a different shape of voxel, that is, isotropic or anisotropic, as well as the volume of a voxel on the volume measurement based on the original image data and multiplanar reconstruction (MPR) data, respectively. In the experiment, we repeatedly acquired contiguous sagittal images of a single globe phantom with a known volume under the condition in which the volume and shape of voxels varied, on a 1.5T MR scanner. We used a gradient echo sequence (3D FLASH). The volume of the globe phantom from both original images and MPR ones was measured on workstations employing a semi-automated local thresholding technique. As a result, the smaller volume of voxels tended to give us the more correct measurement, and an isotropic voxel reduced measurement errors as compared to an anisotropic one. Therefore, it is concluded that the setting of voxel with both an isotropic shape and small volume, e.g., a voxel of 1 mm x 1 mm x 1 mm at present, is recommended in order to get a precise volume measurement using 3D-MRI.